Kevin Struhl

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. pmc MiR-27b targets PPARγ to inhibit growth, tumor progression and the inflammatory response in neuroblastoma cells
    J J Lee
    Department Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Oncogene 31:3818-25. 2012
  2. pmc Determinants of nucleosome positioning
    Kevin Struhl
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA
    Nat Struct Mol Biol 20:267-73. 2013
  3. pmc Rank-statistics based enrichment-site prediction algorithm developed for chromatin immunoprecipitation on chip experiments
    Srinka Ghosh
    Affymetrix Inc, Santa Clara, CA 95051, USA
    BMC Bioinformatics 7:434. 2006
  4. pmc Differential analysis for high density tiling microarray data
    Srinka Ghosh
    Affymetrix Inc, Santa Clara, CA 95051, USA
    BMC Bioinformatics 8:359. 2007
  5. ncbi request reprint Incorporation of Drosophila TAF110 into the yeast TFIID complex does not permit the Sp1 glutamine-rich activation domain to function in vivo
    M Keaveney
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Genes Cells 4:197-203. 1999
  6. ncbi request reprint Transcriptional activation: mediator can act after preinitiation complex formation
    Kevin Struhl
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 17:752-4. 2005
  7. ncbi request reprint Transcriptional noise and the fidelity of initiation by RNA polymerase II
    Kevin Struhl
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Struct Mol Biol 14:103-5. 2007
  8. ncbi request reprint Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity
    Huck Hui Ng
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 11:709-19. 2003
  9. ncbi request reprint The Rtf1 component of the Paf1 transcriptional elongation complex is required for ubiquitination of histone H2B
    Huck Hui Ng
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 278:33625-8. 2003
  10. pmc STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer
    Dimitrios Iliopoulos
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 39:493-506. 2010

Research Grants

Collaborators

Detail Information

Publications127 found, 100 shown here

  1. pmc MiR-27b targets PPARγ to inhibit growth, tumor progression and the inflammatory response in neuroblastoma cells
    J J Lee
    Department Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Oncogene 31:3818-25. 2012
    ..We suggest that the ability of PPARγ to promote or suppress tumor formation is linked to cell type-specific differences in regulation of NHE1 and other target genes...
  2. pmc Determinants of nucleosome positioning
    Kevin Struhl
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA
    Nat Struct Mol Biol 20:267-73. 2013
    ..These determinants influence each other such that the resulting nucleosome positioning patterns are likely to differ among genes and among cells in a population, with consequent effects on gene expression...
  3. pmc Rank-statistics based enrichment-site prediction algorithm developed for chromatin immunoprecipitation on chip experiments
    Srinka Ghosh
    Affymetrix Inc, Santa Clara, CA 95051, USA
    BMC Bioinformatics 7:434. 2006
    ..The detection and assessment of significance for interactions that emanate from non-canonical and/or un-annotated regions of the genome is especially challenging. This is the motivation behind the proposed algorithm...
  4. pmc Differential analysis for high density tiling microarray data
    Srinka Ghosh
    Affymetrix Inc, Santa Clara, CA 95051, USA
    BMC Bioinformatics 8:359. 2007
    ....
  5. ncbi request reprint Incorporation of Drosophila TAF110 into the yeast TFIID complex does not permit the Sp1 glutamine-rich activation domain to function in vivo
    M Keaveney
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Genes Cells 4:197-203. 1999
    ..S. cerevisiae does not contain a homologue of TAF110, suggesting a potential mechanism to account for the failure of glutamine-rich activation domains to stimulate transcription...
  6. ncbi request reprint Transcriptional activation: mediator can act after preinitiation complex formation
    Kevin Struhl
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 17:752-4. 2005
    ..demonstrate that Mediator also has an important role in transcriptional activation after recruitment of the Pol II machinery to promoters...
  7. ncbi request reprint Transcriptional noise and the fidelity of initiation by RNA polymerase II
    Kevin Struhl
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Struct Mol Biol 14:103-5. 2007
    ..This emphasizes the need to develop criteria that distinguish transcriptional noise from transcription with a biological function...
  8. ncbi request reprint Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity
    Huck Hui Ng
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 11:709-19. 2003
    ....
  9. ncbi request reprint The Rtf1 component of the Paf1 transcriptional elongation complex is required for ubiquitination of histone H2B
    Huck Hui Ng
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 278:33625-8. 2003
    ..We suggest that Rtf1 affects genome-wide ubiquitination of H2B by a mechanism that is distinct from its function as a transcriptional elongation factor...
  10. pmc STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer
    Dimitrios Iliopoulos
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 39:493-506. 2010
    ..Thus, STAT3 is not only a downstream target of IL-6 but, with miR-21, miR-181b-1, PTEN, and CYLD, is part of the positive feedback loop that underlies the epigenetic switch that links inflammation to cancer...
  11. pmc Genome-wide mapping indicates that p73 and p63 co-occupy target sites and have similar dna-binding profiles in vivo
    Annie Yang
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA
    PLoS ONE 5:e11572. 2010
    ..The p53 homologs, p63 and p73, share approximately 85% amino acid identity in their DNA-binding domains, but they have distinct biological functions...
  12. pmc Mot1 associates with transcriptionally active promoters and inhibits association of NC2 in Saccharomyces cerevisiae
    Joseph V Geisberg
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 22:8122-34. 2002
    ..We speculate that Mot1 does not form transcriptionally active TBP complexes but rather regulates transcription in vivo by modulating the activity of free TBP and/or by affecting promoter DNA structure...
  13. pmc Targeted recruitment of Rpd3 histone deacetylase represses transcription by inhibiting recruitment of Swi/Snf, SAGA, and TATA binding protein
    Jutta Deckert
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 22:6458-70. 2002
    ..These results suggest that the domain of localized histone deacetylation generated by recruitment of Rpd3 mediates repression by inhibiting recruitment of chromatin-modifying activities and TBP...
  14. pmc Loss of miR-200 inhibition of Suz12 leads to polycomb-mediated repression required for the formation and maintenance of cancer stem cells
    Dimitrios Iliopoulos
    Department Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 39:761-72. 2010
    ..The interaction between miR-200 and Suz12 is highly conserved, suggesting that it represents an ancient regulatory mechanism to control the growth and function of stem cells...
  15. pmc The FACT complex travels with elongating RNA polymerase II and is important for the fidelity of transcriptional initiation in vivo
    Paul B Mason
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell Biol 23:8323-33. 2003
    ..We suggest that FACT contributes to the fidelity of Pol II transcription by linking the processes of initiation and elongation...
  16. pmc Intrinsic histone-DNA interactions are not the major determinant of nucleosome positions in vivo
    Yong Zhang
    Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute and Harvard School of Public Health, Boston, Massachusetts, USA
    Nat Struct Mol Biol 16:847-52. 2009
    ....
  17. ncbi request reprint The transition between transcriptional initiation and elongation in E. coli is highly variable and often rate limiting
    Nikos B Reppas
    Harvard University Biophysics Program, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 24:747-57. 2006
    ..The genomic pattern of RNAP density in E. coli differs from that in yeast and mammalian cells...
  18. ncbi request reprint MAP kinase-mediated stress relief that precedes and regulates the timing of transcriptional induction
    Markus Proft
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Cell 118:351-61. 2004
    ....
  19. ncbi request reprint The transcription factor Ifh1 is a key regulator of yeast ribosomal protein genes
    Joseph T Wade
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 432:1054-8. 2004
    ..Thus, Ifh1 association with promoters is the key regulatory step for coordinate expression of RP genes...
  20. pmc Evidence for eviction and rapid deposition of histones upon transcriptional elongation by RNA polymerase II
    Marc A Schwabish
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell Biol 24:10111-7. 2004
    ....
  21. pmc Akt2 regulates all Akt isoforms and promotes resistance to hypoxia through induction of miR-21 upon oxygen deprivation
    Christos Polytarchou
    Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts 02111, USA
    Cancer Res 71:4720-31. 2011
    ..Taken together, this study identifies a novel Akt2-dependent pathway that is activated by hypoxia and promotes tumor resistance via induction of miR-21...
  22. pmc JNK1 phosphorylation of Cdt1 inhibits recruitment of HBO1 histone acetylase and blocks replication licensing in response to stress
    Benoit Miotto
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 44:62-71. 2011
    ....
  23. pmc Splitting of H3-H4 tetramers at transcriptionally active genes undergoing dynamic histone exchange
    Yael Katan-Khaykovich
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 108:1296-301. 2011
    ..In contrast, tetramer splitting, dimer exchange, and nucleosomes with mixed H3-H4 tetramers occur at highly active genes, presumably linked to rapid histone exchange associated with robust transcription...
  24. ncbi request reprint The stress-activated Hog1 kinase is a selective transcriptional elongation factor for genes responding to osmotic stress
    Markus Proft
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 23:241-50. 2006
    ..Thus, in addition to its various functions during transcriptional initiation, Hog1 behaves as a transcriptional elongation factor that is selective for genes induced upon osmotic stress...
  25. pmc The Swi/Snf complex is important for histone eviction during transcriptional activation and RNA polymerase II elongation in vivo
    Marc A Schwabish
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Mol Cell Biol 27:6987-95. 2007
    ..Taken together, these observations suggest that Swi/Snf is important for histone eviction at enhancers and that it also functions as a Pol II elongation factor...
  26. ncbi request reprint Distinction and relationship between elongation rate and processivity of RNA polymerase II in vivo
    Paul B Mason
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 17:831-40. 2005
    ..Our results suggest that, in vivo, a reduced rate of Pol II elongation leads to premature dissociation along the chromatin template and that Pol II processivity can be uncoupled from elongation rate...
  27. pmc Genomewide identification of Sko1 target promoters reveals a regulatory network that operates in response to osmotic stress in Saccharomyces cerevisiae
    Markus Proft
    Department Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Eukaryot Cell 4:1343-52. 2005
    ....
  28. pmc An HMG protein, Hmo1, associates with promoters of many ribosomal protein genes and throughout the rRNA gene locus in Saccharomyces cerevisiae
    Daniel B Hall
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell Biol 26:3672-9. 2006
    ..We speculate that Hmo1 has a role in coordinating the transcription of rRNA and RP genes...
  29. pmc Extensive chromatin fragmentation improves enrichment of protein binding sites in chromatin immunoprecipitation experiments
    Xiaochun Fan
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Nucleic Acids Res 36:e125. 2008
    ..We show that many yeast promoter regions are virtually devoid of histones...
  30. ncbi request reprint Cellular stress alters the transcriptional properties of promoter-bound Mot1-TBP complexes
    Joseph V Geisberg
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 14:479-89. 2004
    ..This suggests that functional preinitiation complexes can contain Mot1 instead of TFIIA in vivo. Thus, Mot1-TBP complexes can exist in active and inactive forms that are regulated by environmental stress...
  31. ncbi request reprint Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation
    Amita A Joshi
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 20:971-8. 2005
    ....
  32. pmc Eaf3 regulates the global pattern of histone acetylation in Saccharomyces cerevisiae
    Juliet L Reid
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell Biol 24:757-64. 2004
    ..We suggest that Eaf3 regulates the genomic profile of histone H3 and H4 acetylation in a manner that does not involve targeted recruitment and is independent of transcriptional activity...
  33. pmc Genome-wide occupancy profile of the RNA polymerase III machinery in Saccharomyces cerevisiae reveals loci with incomplete transcription complexes
    Zarmik Moqtaderi
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 24:4118-27. 2004
    ..Furthermore, the unusual profile of Pol III factor association with ZOD1 and the ETC loci is perfectly preserved in a different Saccharomyces species, indicating that these loci represent novel functional entities...
  34. pmc Genomic binding profiles of functionally distinct RNA polymerase III transcription complexes in human cells
    Zarmik Moqtaderi
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA
    Nat Struct Mol Biol 17:635-40. 2010
    ..Our results suggest that human Pol III complexes associate preferentially with regions near functional Pol II promoters and that TFIIIC-mediated recruitment of TFIIIB is regulated in a locus-specific manner...
  35. pmc TFIIH phosphorylation of the Pol II CTD stimulates mediator dissociation from the preinitiation complex and promoter escape
    Koon Ho Wong
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA Faculty of Health Sciences, University of Macau, Macau SAR, China
    Mol Cell 54:601-12. 2014
    ..These observations suggest that TFIIH phosphorylation of the CTD causes Mediator dissociation, thereby permitting rapid promoter escape of Pol II from the preinitiation complex. ..
  36. pmc Heterochromatin formation involves changes in histone modifications over multiple cell generations
    Yael Katan-Khaykovich
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    EMBO J 24:2138-49. 2005
    ..Thus, the transition between euchromatin and heterochromatin is gradual and requires multiple cell division cycles...
  37. pmc Histone H3R2 symmetric dimethylation and histone H3K4 trimethylation are tightly correlated in eukaryotic genomes
    Chih Chi Yuan
    Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA
    Cell Rep 1:83-90. 2012
    ..Our work suggests that H3R2me2sK4me3, not simply H3K4me3 alone, is the mark of active promoters and that factors that recognize H3K4me3 will have their binding modulated by their preference for H3R2me2s...
  38. pmc An integrated transcriptional regulatory circuit that reinforces the breast cancer stem cell state
    Christos Polytarchou
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 109:14470-5. 2012
    ....
  39. pmc Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: a potential mechanism for position-effect variegation
    Huck Hui Ng
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:1820-5. 2003
    ..This positive feedback loop, and the reverse loop in which H3-K79 methylation weakens Sir protein association and leads to further methylation, suggests a model for position-effect variegation...
  40. pmc Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types
    Dimitrios Iliopoulos
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA
    Cancer Res 71:3196-201. 2011
    ....
  41. pmc Genomic analysis of LexA binding reveals the permissive nature of the Escherichia coli genome and identifies unconventional target sites
    Joseph T Wade
    Department of Biological Chemistry and Molecular Pharmacology, Harvard University, Boston, Massachusetts 02115, USA
    Genes Dev 19:2619-30. 2005
    ..coli genome is permissive to transcription factor binding. The permissive nature of the E. coli genome has important consequences for the nature of transcriptional regulatory proteins, biological specificity, and evolution...
  42. ncbi request reprint Asf1 mediates histone eviction and deposition during elongation by RNA polymerase II
    Marc A Schwabish
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 22:415-22. 2006
    ..Lastly, Asf1 inhibits internal initiation from cryptic promoters within coding regions. These results strongly suggest that Asf1 functions as an elongation factor to disassemble and reassemble histones during Pol II elongation...
  43. pmc Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association
    Huck Hui Ng
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 16:1518-27. 2002
    ..Our results indicate that histone modifications in the core globular domain have important biological functions...
  44. ncbi request reprint Genomic analysis of protein-DNA interactions in bacteria: insights into transcription and chromosome organization
    Joseph T Wade
    Department of Biological Chemistry and Molecular Pharmacology, Harvard University, Boston, MA 02115, USA
    Mol Microbiol 65:21-6. 2007
    ..Here we review recent applications of ChIP-chip to the study of bacteria, which provide important and unexpected insights into transcription and chromosome organization...
  45. ncbi request reprint The histone H3-like TAF is broadly required for transcription in yeast
    Z Moqtaderi
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 2:675-82. 1998
    ....
  46. ncbi request reprint Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells
    Annie Yang
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 24:593-602. 2006
    ..Many p63 binding regions are evolutionarily conserved and/or associated with sequence motifs for other transcription factors, suggesting that a substantial portion of p63 sites is biologically relevant...
  47. pmc Differential gene regulation by selective association of transcriptional coactivators and bZIP DNA-binding domains
    Benoit Miotto
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell Biol 26:5969-82. 2006
    ..Thus, the bZIP domain mediates selective interactions with coactivators and hence differential regulation of gene expression...
  48. pmc Where does mediator bind in vivo?
    Xiaochun Fan
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA
    PLoS ONE 4:e5029. 2009
    ..In contrast, whole genome microarray experiments in synthetic complete (SC) medium reported that Mediator associates with many genes at both promoter and coding regions...
  49. pmc NF-Y coassociates with FOS at promoters, enhancers, repetitive elements, and inactive chromatin regions, and is stereo-positioned with growth-controlling transcription factors
    Joseph D Fleming
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genome Res 23:1195-209. 2013
    ..Our results indicate that NF-Y is not merely a commonly used proximal promoter TF, but rather performs a more diverse set of biological functions, many of which are likely to involve coassociation with FOS. ..
  50. pmc Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth
    Heather A Hirsch
    Department Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 110:972-7. 2013
    ..As metformin alters energy metabolism in diabetics, we speculate that metformin may block a metabolic stress response that stimulates the inflammatory pathway associated with a wide variety of cancers...
  51. pmc Nucleosome depletion at yeast terminators is not intrinsic and can occur by a transcriptional mechanism linked to 3'-end formation
    Xiaochun Fan
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:17945-50. 2010
    ....
  52. doi request reprint Defining in vivo targets of nuclear proteins by chromatin immunoprecipitation and microarray analysis
    Zarmik Moqtaderi
    Harvard Medical School, Boston, Massachusetts, USA
    Curr Protoc Mol Biol . 2004
    ..This method allows the study of a protein's pattern of DNA association across an entire genome with no need for prior knowledge of potential DNA targets...
  53. ncbi request reprint Ubiquitination of histone H2B by Rad6 is required for efficient Dot1-mediated methylation of histone H3 lysine 79
    Huck Hui Ng
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 277:34655-7. 2002
    ..Our study provides a new example of trans-histone regulation between modifications on different histones. In addition, it suggests that Rad6 affects telomeric silencing, at least in part, by influencing methylation of histone H3...
  54. pmc Inhibition of miR-193a expression by Max and RXRα activates K-Ras and PLAU to mediate distinct aspects of cellular transformation
    Dimitrios Iliopoulos
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA
    Cancer Res 71:5144-53. 2011
    ....
  55. ncbi request reprint Hog1 kinase converts the Sko1-Cyc8-Tup1 repressor complex into an activator that recruits SAGA and SWI/SNF in response to osmotic stress
    Markus Proft
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 9:1307-17. 2002
    ..Cyc8-Tup1 is not simply a corepressor but is also involved in recruiting SWI/SNF and SAGA during the transcriptional induction process...
  56. ncbi request reprint Extensive functional overlap between sigma factors in Escherichia coli
    Joseph T Wade
    Department of Biological Chemistry and Molecular Pharmacology, Harvard University, Boston, Massachusetts 02115, USA
    Nat Struct Mol Biol 13:806-14. 2006
    ..SigmaE-regulated promoters also overlap extensively with those for sigma70. These results suggest that extensive functional overlap between sigma factors is an important phenomenon...
  57. ncbi request reprint TAF-Containing and TAF-independent forms of transcriptionally active TBP in vivo
    L Kuras
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Science 288:1244-8. 2000
    ..Promoter-specific variations in the association of these distinct forms of TBP may explain why only some yeast genes require TFIID for transcriptional activity in vivo...
  58. ncbi request reprint Activator-specific recruitment of Mediator in vivo
    Xiaochun Fan
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Struct Mol Biol 13:117-20. 2006
    ..Mediator is recruited by many activators involved in stress responses, but not by the major activators that function under optimal conditions...
  59. ncbi request reprint Activator-specific recruitment of TFIID and regulation of ribosomal protein genes in yeast
    Mario Mencía
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 9:823-33. 2002
    ..These results demonstrate activator-specific recruitment of TFIID in vivo, and they suggest that TFIID recruitment is important for coordinate expression of RP genes...
  60. pmc Species-specific factors mediate extensive heterogeneity of mRNA 3' ends in yeasts
    Zarmik Moqtaderi
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 110:11073-8. 2013
    ..In S. cerevisiae strains, D. hansenii genes adopt the S. cerevisiae polyadenylation profile, indicating that the polyadenylation pattern is mediated primarily by species-specific factors. ..
  61. doi request reprint Expanding the repertoire of plasmids for PCR-mediated epitope tagging in yeast
    Zarmik Moqtaderi
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Yeast 25:287-92. 2008
    ..For all the tagged alleles, ChIP occupancy signals are easily detectable at known Tfc6 target genes. These new tags provide additional options in experimental schemes requiring multiple tagged proteins...
  62. pmc HBO1 histone acetylase is a coactivator of the replication licensing factor Cdt1
    Benoit Miotto
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 22:2633-8. 2008
    ..As HBO1 is also a transcriptional coactivator, it has the potential to integrate internal and external stimuli to coordinate transcriptional responses with initiation of DNA replication...
  63. pmc Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion
    Dimitrios Iliopoulos
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 108:1397-402. 2011
    ..This dynamic equilibrium provides an additional rationale for combining conventional chemotherapy with metformin, which selectively inhibits CSCs...
  64. ncbi request reprint Intrinsic histone-DNA interactions and low nucleosome density are important for preferential accessibility of promoter regions in yeast
    Edward A Sekinger
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 18:735-48. 2005
    ..This organization ensures that transcription factors bind preferentially to appropriate sites in promoters, rather than to the excess of irrelevant sites in nonpromoter regions...
  65. ncbi request reprint Binding of TBP to promoters in vivo is stimulated by activators and requires Pol II holoenzyme
    L Kuras
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 399:609-13. 1999
    ....
  66. pmc Genome-wide location and regulated recruitment of the RSC nucleosome-remodeling complex
    Huck Hui Ng
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 16:806-19. 2002
    ..Therefore, the RSC complex is generally recruited to Pol III promoters and it is specifically recruited to Pol II promoters by transcriptional activators and repressors...
  67. pmc Chipper: discovering transcription-factor targets from chromatin immunoprecipitation microarrays using variance stabilization
    Francis D Gibbons
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Longwood Avenue, Boston, MA 02115, USA
    Genome Biol 6:R96. 2005
    ..The corresponding software ('Chipper') is freely available. The method described here should help reveal an organism's transcription-regulatory 'wiring diagram'...
  68. ncbi request reprint [Histone H4 lysine 16 acetylation: from genome regulation to tumoral progression]
    Benoit Miotto
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Med Sci (Paris) 23:735-40. 2007
    ..Recent discoveries highlight its crucial involvement in events such as transcription regulation, chromatin specialization, chromosome compaction and tumoral progression...
  69. pmc The Cyc8-Tup1 complex inhibits transcription primarily by masking the activation domain of the recruiting protein
    Koon Ho Wong
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 25:2525-39. 2011
    ..We suggest that the corepressor function of Cyc8-Tup1 makes only a modest contribution to expression of target genes, specifically to keep expression levels below the nonactivated state...
  70. pmc HBO1 histone acetylase activity is essential for DNA replication licensing and inhibited by Geminin
    Benoit Miotto
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 37:57-66. 2010
    ..Thus, H4 acetylation at origins by HBO1 is critical for replication licensing by Cdt1, and negative regulation of licensing by Geminin is likely to involve inhibition of HBO1 histone acetylase activity...
  71. pmc Yeast NC2 associates with the RNA polymerase II preinitiation complex and selectively affects transcription in vivo
    J V Geisberg
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 21:2736-42. 2001
    ..Thus, NC2 is associated with the Pol II preinitiation complex, and it can play a direct and positive role at certain promoters in vivo...
  72. pmc An HNF4α-miRNA inflammatory feedback circuit regulates hepatocellular oncogenesis
    Maria Hatziapostolou
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 147:1233-47. 2011
    ..As we also show that this HNF4α circuit is perturbed in human hepatocellular carcinomas, our data raise the possibility that manipulation of this microRNA feedback-inflammatory loop has therapeutic potential for treating liver cancer...
  73. ncbi request reprint The VP16 activation domain interacts with multiple transcriptional components as determined by protein-protein cross-linking in vivo
    Daniel B Hall
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 277:46043-50. 2002
    ..We show that the VP16 activation domain directly interacts with TATA-binding protein (TBP), TFIIB, and the SAGA histone acetylase complex in vivo...
  74. pmc An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation
    Dimitrios Iliopoulos
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Cell 139:693-706. 2009
    ..Thus, inflammation activates a positive feedback loop that maintains the epigenetic transformed state for many generations in the absence of the inducing signal...
  75. pmc A transcriptional signature and common gene networks link cancer with lipid metabolism and diverse human diseases
    Heather A Hirsch
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 17:348-61. 2010
    ..We suggest that the interplay between this common transcriptional program and cell-type-specific factors gives rise to phenotypically disparate human diseases...
  76. pmc Quantitative sequential chromatin immunoprecipitation, a method for analyzing co-occupancy of proteins at genomic regions in vivo
    Joseph V Geisberg
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Nucleic Acids Res 32:e151. 2004
    ..Our quantitative treatment of SeqChIP data substantially expands the usefulness of the technique for elucidating molecular mechanisms in vivo...
  77. doi request reprint Analysis of protein co-occupancy by quantitative sequential chromatin immunoprecipitation
    Joseph V Geisberg
    Harvard Medical School, Boston, Massachusetts, USA
    Curr Protoc Mol Biol . 2005
    ..In principle, the technique is not limited to Saccharomyces cerevisiae. Cells from a wide variety of organisms can be used...
  78. pmc Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission
    Heather A Hirsch
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02115, USA
    Cancer Res 69:7507-11. 2009
    ....
  79. ncbi request reprint The TBP-TFIIA interaction in the response to acidic activators in vivo
    L A Stargell
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Science 269:75-8. 1995
    ..Fusion of the small subunit of TFIIA to N2-1 restores activation function in vivo. Thus, an efficient interaction between TBP and TFIIA is required for transcriptional activation in vivo...
  80. pmc Yeast GCN4 transcriptional activator protein interacts with RNA polymerase II in vitro
    C J Brandl
    Department of Biological Chemistry, Harvard Medical School, Boston, MA 02115
    Proc Natl Acad Sci U S A 86:2652-6. 1989
    ..Using deletion mutants, we also show that the DNA-binding domain of GCN4 is both necessary and sufficient for this interaction. We suggest the possibility that this GCN4-Pol II interaction may be important for transcription in vivo...
  81. ncbi request reprint The TATA-binding protein is required for transcription by all three nuclear RNA polymerases in yeast cells
    B P Cormack
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115
    Cell 69:685-96. 1992
    ..These observations suggest that TBP is required for transcription of all nuclearly encoded genes in yeast, although distinct molecular mechanisms are probably involved for the three RNA polymerase transcription machineries...
  82. ncbi request reprint Regional codon randomization: defining a TATA-binding protein surface required for RNA polymerase III transcription
    B P Cormack
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115
    Science 262:244-8. 1993
    ....
  83. ncbi request reprint The TAFs in the HAT
    K Struhl
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 94:1-4. 1998
  84. pmc Multiple functions of the nonconserved N-terminal domain of yeast TATA-binding protein
    M Lee
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Genetics 158:87-93. 2001
    ..It inhibits the interaction of TBP with TATA elements, and it acts positively in combination with a specific region of the TBP core domain that presumably interacts with another protein(s)...
  85. pmc A new class of activation-defective TATA-binding protein mutants: evidence for two steps of transcriptional activation in vivo
    L A Stargell
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 16:4456-64. 1996
    ..Thus, these TBP mutants define two steps in the process of transcriptional stimulation by acidic activators: efficient recruitment to the TATA element and a postrecruitment interaction with a component(s) of the initiation complex...
  86. pmc Region of yeast TAF 130 required for TFIID to associate with promoters
    M Mencia
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 21:1145-54. 2001
    ..These results suggest that the C-terminal region of TAF130 is required for TFIID to associate with promoters...
  87. pmc Association of RNA polymerase with transcribed regions in Escherichia coli
    Joseph T Wade
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 101:17777-82. 2004
    ..These observations suggest that in vivo association of sigma(70) and NusA with elongating RNAP is regulated by growth conditions...
  88. pmc Nucleosome positioning signals in genomic DNA
    Heather E Peckham
    Bioinformatics Program, Boston University, Boston, MA 02215, USA
    Genome Res 17:1170-7. 2007
    ..Finally, we show that intrinsic nucleosome positioning signals are both more inhibitory and more variable in promoter regions than in open reading frames in S. cerevisiae...
  89. pmc Transcriptional activation by TFIIB mutants that are severely impaired in interaction with promoter DNA and acidic activation domains
    S Chou
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 17:6794-802. 1997
    ..However, one TFIIB derivative shows reduced transcription of GAL4, suggesting that TFIIB may be limiting at a subset of promoters in vivo...
  90. pmc CDC39, an essential nuclear protein that negatively regulates transcription and differentially affects the constitutive and inducible HIS3 promoters
    M A Collart
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115
    EMBO J 12:177-86. 1993
    ..These observations suggest that CDC39 negatively regulates transcription either by affecting the general RNA polymerase II machinery or by altering chromatin structure...
  91. ncbi request reprint Mechanisms of transcriptional activation in vivo: two steps forward
    L A Stargell
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Trends Genet 12:311-5. 1996
    ..TFIID binding is then followed by the recruitment of the remainder of the transcriptional apparatus in the form of the RNA polymerase II holoenzyme...
  92. pmc Dynamics of global histone acetylation and deacetylation in vivo: rapid restoration of normal histone acetylation status upon removal of activators and repressors
    Yael Katan-Khaykovich
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 16:743-52. 2002
    ..Our results also indicate that TBP occupancy depends on the presence of the activator, not histone acetylation status...
  93. pmc Preferential accessibility of the yeast his3 promoter is determined by a general property of the DNA sequence, not by specific elements
    X Mai
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 20:6668-76. 2000
    ....
  94. pmc Yeast homologues of higher eukaryotic TFIID subunits
    Z Moqtaderi
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 93:14654-8. 1996
    ..Yeast TAF61 is significantly larger than its higher eukaryotic homologues, and deletion analysis demonstrates that the evolutionarily conserved, histone-like domain is sufficient and necessary to support viability...
  95. pmc Targeted recruitment of the Sin3-Rpd3 histone deacetylase complex generates a highly localized domain of repressed chromatin in vivo
    D Kadosh
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 18:5121-7. 1998
    ..Taken together with previous observations, these results define a novel mechanism of transcriptional repression which involves targeted recruitment of a histone-modifying activity and localized perturbation of chromatin structure...
  96. ncbi request reprint NOT1(CDC39), NOT2(CDC36), NOT3, and NOT4 encode a global-negative regulator of transcription that differentially affects TATA-element utilization
    M A Collart
    Department of Biological Chemistry, Harvard Medical School, Boston, Massachusetts 02115
    Genes Dev 8:525-37. 1994
    ..We propose that the NOT protein inhibit the basic RNA polymerase II transcription machinery, possibly by affecting TFIID function...
  97. ncbi request reprint Repression by Ume6 involves recruitment of a complex containing Sin3 corepressor and Rpd3 histone deacetylase to target promoters
    D Kadosh
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 89:365-71. 1997
    ..Rpd3 is specifically required for repression by Sin3, and artificial recruitment of Rpd3 results in repression. These results suggest that repression by Ume6 involves recruitment of a Sin3-Rpd3 complex and targeted histone deacetylation...
  98. pmc TFIIS enhances transcriptional elongation through an artificial arrest site in vivo
    D Kulish
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 21:4162-8. 2001
    ....
  99. pmc Genetic analysis of the role of Pol II holoenzyme components in repression by the Cyc8-Tup1 corepressor in yeast
    M Lee
    Departments of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genetics 155:1535-42. 2000
    ..Genetic interactions among srb mutations imply that a balance between the activities of Srb8 + Srb10 and Srb11 is important for normal cell growth...
  100. pmc Association of distinct yeast Not2 functional domains with components of Gcn5 histone acetylase and Ccr4 transcriptional regulatory complexes
    J D Benson
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    EMBO J 17:6714-22. 1998
    ....
  101. pmc GCN4, a eukaryotic transcriptional activator protein, binds as a dimer to target DNA
    I A Hope
    Department of Biological Chemistry, Harvard Medical School, Boston, MA 02115
    EMBO J 6:2781-4. 1987
    ..These observations suggest a structural model of GCN4 protein in which a dimer binds to overlapping and non-identical half-sites, explaining why GCN4 recognition sites act bidirectionally in stimulating transcription...

Research Grants1

  1. Molecular Mechanisms of Global Represion in Yeast
    Kevin Struhl; Fiscal Year: 2008
    ..We will use RNAi to identify genes affected by the various TLE proteins, and will address the mechanism of repression by TLE proteins by using derivatives of the well characterized B-interferon promoter. ..