Research Topics
Genomes and Genes | Shelley L BergerSummaryAffiliation: The Wistar Institute Country: USA Publications
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The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expressionEfrat Shema
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel
Genes Dev 22:2664-76. 2008..Furthermore, frequent RNF20 promoter hypermethylation was observed in tumors. RNF20 may thus be a putative tumor suppressor, acting through selective regulation of a distinct subset of genes...
The complex language of chromatin regulation during transcriptionShelley L Berger
The Wistar Institute, 3601 Spruce Street, Room 201, Philadelphia, Pennsylvania 19104, USA
Nature 447:407-12. 2007..Although such modifications were initially thought to be a simple code, a more likely model is of a sophisticated, nuanced chromatin 'language' in which different combinations of basic building blocks yield dynamic functional outcomes...
Out of the jaws of death: PRMT5 steers p53Shelley L Berger
The Wistar Institute, Gene Expression and Regulation Program, 3601 Spruce Street, Room 201, Philadelphia, Pennsylvania 19104, USA
Nat Cell Biol 10:1389-90. 2008..Now, arginine methylation joins a panoply of other post-translational modifications that regulate p53. PRMT5 mediates p53 methylation, which disposes the cell to arrest rather than death...
Histone H3 K4 demethylation during activation and attenuation of GAL1 transcription in Saccharomyces cerevisiaeKristin Ingvarsdottir
Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
Mol Cell Biol 27:7856-64. 2007..Thus, analysis of lysine demethylation in yeast provides new insight into the physiological roles of jumonji demethylase enzymes...
Maintenance of low histone ubiquitylation by Ubp10 correlates with telomere-proximal Sir2 association and gene silencingN C Tolga Emre
Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, PA 19024, USA
Mol Cell 17:585-94. 2005..Our results suggest that these H2B-deubiquitylating enzymes have distinct genomic functions...
H2B ubiquitylation acts as a barrier to Ctk1 nucleosomal recruitment prior to removal by Ubp8 within a SAGA-related complexAnastasia Wyce
Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, PA 19104, USA
Mol Cell 27:275-88. 2007..These findings reveal a mechanism by which H2B ubiquitylation acts as a barrier to Ctk1 association with active genes, while subsequent deubiquitylation by Ubp8 triggers Ctk1 recruitment at the appropriate point in activation...
Histone H4 lysine 16 acetylation regulates cellular lifespanWeiwei Dang
Gene Expression and Regulation Program, The Wistar Institute Philadelphia, Pennsylvania 19104, USA
Nature 459:802-7. 2009..This pathway, distinct from existing ageing models for yeast, may represent an evolutionarily conserved function of sirtuins in regulation of replicative ageing by maintenance of intact telomeric chromatin...
Genome-wide mapping of histone H4 serine-1 phosphorylation during sporulation in Saccharomyces cerevisiaeJerome Govin
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
Nucleic Acids Res 38:4599-606. 2010..These studies indicate distinctive features of a histone H4 modification marking system during sporulation compared with DSB repair...
SALSA, a variant of yeast SAGA, contains truncated Spt7, which correlates with activated transcriptionDavid E Sterner
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 99:11622-7. 2002..These data clarify a mechanism by which a transcriptional regulatory complex can switch between positive and negative modulation...
Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated Ubp8Karl W Henry
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
Genes Dev 17:2648-63. 2003..These results suggest that the histone H2B ubiquitylation state is dynamic during transcription, and that the sequence of histone modifications helps to control transcription...
Inactivation of the Sas2 histone acetyltransferase delays senescence driven by telomere dysfunctionMarina L Kozak
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6100, USA
EMBO J 29:158-70. 2010..In contrast, sir4 deletion sped senescence and blocked the delay conferred by sas2 or sir3 deletion. We thus show that manipulation of telomere chromatin modulates senescence caused by telomere shortening...
Histone modification patterns during gene activationWan-Sheng Lo
Wistar Institute, Philadelphia, Pennsylvania 19104, USA
Methods Enzymol 377:130-53. 2004
Histone sumoylation is a negative regulator in Saccharomyces cerevisiae and shows dynamic interplay with positive-acting histone modificationsDafna Nathan
Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
Genes Dev 20:966-76. 2006..These results indicate that sumoylation is the first negative histone modification to be identified in S. cerevisiae and further suggest that sumoylation may serve as a general dynamic mark to oppose transcription...
Signaling kinase AMPK activates stress-promoted transcription via histone H2B phosphorylationDavid Bungard
Department of Cellular and Developmental Biology, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA
Science 329:1201-5. 2010..Our results place AMPK-dependent H2B Ser36 phosphorylation in a direct transcriptional and chromatin regulatory pathway leading to cellular adaptation to stress...
CTCF-dependent chromatin boundary element between the latency-associated transcript and ICP0 promoters in the herpes simplex virus type 1 genomeQi Chen
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
J Virol 81:5192-201. 2007....
The histone variant H3.3 regulates gene expression during lytic infection with herpes simplex virus type 1Brandon J Placek
Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennysylvania 19104, USA
J Virol 83:1416-21. 2009..These findings show that incorporation of H3.3 facilitates transcription, and they provide new evidence for a regulatory role of chromatin composition during HSV-1 acute infection...
H2B ubiquitin protease Ubp8 and Sgf11 constitute a discrete functional module within the Saccharomyces cerevisiae SAGA complexKristin Ingvarsdottir
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
Mol Cell Biol 25:1162-72. 2005..These data indicate that Ubp8 and Sgf11 likely represent a new functional module within SAGA that is involved in gene regulation through H2B deubiquitylation...
Good fences make good neighbors: barrier elements and genomic regulationJumin Zhou
The Wistar Institute, Philadelphia, Pennsylvania 19014, USA
Mol Cell 16:500-2. 2004..In a recent issue of Molecular Cell, West et al. (2004) shed light on mechanisms underlying these molecular "fences."..
Systematic screen reveals new functional dynamics of histones H3 and H4 during gametogenesisJerome Govin
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
Genes Dev 24:1772-86. 2010..Thus, our results show that investigation of gametogenesis in yeast provides novel insights into chromatin dynamics, which are potentially relevant to epigenetic modulation of the mammalian process...
Histone H4 lysine 20 of Saccharomyces cerevisiae is monomethylated and functions in subtelomeric silencingChristopher R Edwards
Department of Cellular and Developmental Biology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
Biochemistry 50:10473-83. 2011..Our findings reveal the first negative regulatory histone methylation in budding yeast and indicate that H4 K20me1 is evolutionarily conserved from simple to complex eukaryotes...
The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progressionXiao Yong Zhang
The Department of Cancer Biology, The Kimmel Cancer Center, Thomas Jefferson Medical College, Philadelphia, PA 19107, USA
Mol Cell 29:102-11. 2008..In support of a functional role within the Polycomb/cancer stem cell signature, USP22 is required for appropriate progression through the cell cycle...
Structure and dimerization of the kinase domain from yeast Snf1, a member of the Snf1/AMPK protein familyVinod Nayak
The Wistar Institute, University of Pennsylvania, Philadelphia 19104, USA
Structure 14:477-85. 2006..Taken together, these studies suggest another layer of kinase regulation within the Snf1/AMPK family, and an avenue for development of AMPK-specific activating compounds...
p53 is regulated by the lysine demethylase LSD1Jing Huang
The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA
Nature 449:105-8. 2007..Lysine methylation therefore provides similar regulatory complexity for non-histone proteins and for histones...
The linker histone plays a dual role during gametogenesis in Saccharomyces cerevisiaeJessica M Bryant
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Mol Cell Biol 32:2771-83. 2012....
Structural basis for histone and phosphohistone binding by the GCN5 histone acetyltransferaseAdrienne Clements
The Wistar Institute, Philadelphia, PA 19104, USA
Mol Cell 12:461-73. 2003..Together, these studies reveal how one histone modification can modulate another to affect distinct transcriptional signals...
Chromatin dynamics during herpes simplex virus-1 lytic infectionBrandon J Placek
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
Biochim Biophys Acta 1799:223-7. 2010..Here we discuss recent studies that underscore the importance of chromatin regulation during the lytic phase of the HSV-1 life-cycle...
Trimethylation of histone H3 lysine 4 by Set1 in the lytic infection of human herpes simplex virus 1Jing Huang
The Wistar Institute, Philadelphia, PA 19104, USA
J Virol 80:5740-6. 2006....
Sumoylation of the yeast Gcn5 proteinDavid E Sterner
Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
Biochemistry 45:1035-42. 2006..Taken together with recent identification of multiple additional subunits of SAGA as sumoylated proteins in vivo, these data suggest that Gcn5 sumoylation may have an inhibitory role in transcriptional regulation...
Repression of p53 activity by Smyd2-mediated methylationJing Huang
Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
Nature 444:629-32. 2006..Thus, similar to histones, p53 is subject to both activating and repressing lysine methylation. Our results also predict that Smyd2 may function as a putative oncogene by methylating p53 and repressing its tumour suppressive function...
Histone modifications in transcriptional regulationShelley L Berger
The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA
Curr Opin Genet Dev 12:142-8. 2002..This multiplicity of modifications, and their occurrence in patterns and dependent sequences, argues persuasively for the existence of a histone code...
Histone modifications: Now summoning sumoylationDafna Nathan
Gene Expression and Regulation Program, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 100:13118-20. 2003
Identification and characterization of novel sirtuin inhibitor scaffoldsBrandi D Sanders
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
Bioorg Med Chem 17:7031-41. 2009....
H2B ubiquitylation and de-ubiquitylation in gene activationAnastasia Wyce
The Wistar Institute, Gene Expression and Regulation Program, 3601 Spruce Street, Philadelphia, PA 19104, USA
Novartis Found Symp 259:63-73; discussion 73-7, 163-9. 2004..These results suggest that ubiquitylation of histones has a unique role among histone modifications, possibly to orchestrate an ordered pathway of chromatin alterations...
MYST protein acetyltransferase activity requires active site lysine autoacetylationHua Yuan
Gene Expression and Regulation Program, The Wistar Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
EMBO J 31:58-70. 2012..These findings provide an avenue for the autoposttranslational regulation of MYST proteins that is distinct from other acetyltransferases but draws similarities to the phosphoregulation of protein kinases...
A novel human Ada2 homologue functions with Gcn5 or Brg1 to coactivate transcriptionNickolai A Barlev
Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania, USA
Mol Cell Biol 23:6944-57. 2003....
Phosphorylation of histone H4 Ser1 regulates sporulation in yeast and is conserved in fly and mouse spermatogenesisThanuja Krishnamoorthy
Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
Genes Dev 20:2580-92. 2006..Thus, H4 S1ph may be an evolutionarily ancient histone modification to mark the genome for gamete-associated packaging...
Hit and run: transient deubiquitylase activity in a chromatin-remodeling complexValerie P Zediak
Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, PA 19104, USA
Mol Cell 31:773-4. 2008..2008) provide a glimpse into an interesting mechanism to control a deubiquitylating enzyme via interaction of two complexes-the 19S proteasome regulatory particle and an ATP-dependent nucleosome remodeling complex...
The emerging field of dynamic lysine methylation of non-histone proteinsJing Huang
Gene Expression and Regulation Program, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19087, United States
Curr Opin Genet Dev 18:152-8. 2008..Taking into account combinatorial activity with numerous other PTMs, lysine methylation provides enormous functional diversity and regulatory complexity...
In vivo dual cross-linking for identification of indirect DNA-associated proteins by chromatin immunoprecipitationPing-Yao Zeng
The Wistar Institute, Philadelphia, PA 19104, USA
Biotechniques 41:694, 696, 698. 2006
Genome reprogramming during sporulationJerome Govin
Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, PA19104, USA
Int J Dev Biol 53:425-32. 2009..Here, we review how chromatin structure and genome reprogramming regulate the sporulation transcription program, and how post-meiotic events reorganize spore chromatin...
Temporal and spatial changes in transcription factor binding and histone modifications at the steroidogenic acute regulatory protein (stAR) locus associated with stAR transcriptionHisahiko Hiroi
Center for Research on Reproduction and Women s Health, University of Pennsylvania Medical Center, 1354 Biomedical Research Building, 421 Curie Boulevard, Philadelphia, PA 19104, USA
Mol Endocrinol 18:791-806. 2004..Our findings demonstrate that increased StAR transcription can occur in the context of different patterns of transcription factor binding and histone modification...
Cutting edge: persistently open chromatin at effector gene loci in resting memory CD8+ T cells independent of transcriptional statusValerie P Zediak
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
J Immunol 186:2705-9. 2011..We propose that these chromatin changes poise effector genes for rapid upregulation, but are insufficient for PolII recruitment and transcription...
An operational definition of epigeneticsShelley L Berger
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Genes Dev 23:781-3. 2009..It was evident that multiple mechanistic steps lead to the stable heritance of the epigenetic phenotype. Below we provide our view and interpretation of the proceedings at the meeting...
LKB1 is recruited to the p21/WAF1 promoter by p53 to mediate transcriptional activationPing Yao Zeng
Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania and Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan Province, P R China
Cancer Res 66:10701-8. 2006..Finally, a genetic fusion of LKB1 to defective p53, deleted for its activation domains, promotes activation of p21/WAF1. These results indicate that LKB1 has a direct role in activation of p21/WAF1 gene...
The SANT domain of Ada2 is required for normal acetylation of histones by the yeast SAGA complexDavid E Sterner
Wistar Institute, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 277:8178-86. 2002..These results suggest that histone and nucleosomal substrate recognition by SAGA involves multiple conserved domains and proteins, beyond those that have been previously identified...
A feed-forward repression mechanism anchors the Sin3/histone deacetylase and N-CoR/SMRT corepressors on chromatinMichiel Vermeulen
NCMLS, Radboud University Nijmegen, Department of Molecular Biology, Geert Grooteplein Zuid 30, Nijmegen, The Netherlands
Mol Cell Biol 26:5226-36. 2006....
Trans-tail histone modifications: wedge or bridge?Karl W Henry
Nat Struct Biol 9:565-6. 2002
Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction mapSean R Collins
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA
Nature 446:806-10. 2007..This modification, in turn, enables a ubiquitin ligase complex containing the cullin Rtt101 to ensure genomic integrity during DNA replication...
Activating signal cointegrator 2 belongs to a novel steady-state complex that contains a subset of trithorax group proteinsYoung Hwa Goo
Department of Life Science, Pohang University of Science and Technology, Korea
Mol Cell Biol 23:140-9. 2003..Further characterization of ASCOM will lead to a better understanding of how nuclear receptors and other transcription factors mediate transcriptional activation...
New nomenclature for chromatin-modifying enzymesC David Allis
Cell 131:633-6. 2007
14-3-3 interaction with histone H3 involves a dual modification pattern of phosphoacetylationWendy Walter
Division of Molecular Genetics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3 QU, United Kingdom
Mol Cell Biol 28:2840-9. 2008..The importance of acetylation in this interaction is also seen in vivo, where K14 acetylation is required for optimal Bmh1 recruitment to the GAL1 promoter during transcriptional activation...
Phosphorylation of histone H4 serine 1 during DNA damage requires casein kinase II in S. cerevisiaeWang L Cheung
Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland 21210, USA
Curr Biol 15:656-60. 2005..CK2 has been implicated in regulating a DNA-damage response; our data suggest that histone H4 S1 is one of its physiological substrates. These data suggest that this modification is a part of the DNA-repair histone code...
Histone H3 phosphorylation can promote TBP recruitment through distinct promoter-specific mechanismsWan Sheng Lo
Division of Biological Sciences and UCSD Cancer Center, University of California, San Diego, CA, USA
EMBO J 24:997-1008. 2005..Our results emphasize that histone modifications share general functions between promoters, but also acquire distinct roles tailored for promoter-specific requirements...
Research Grants
- The Enzymology of Chromatin and TranscriptionShelley Berger; Fiscal Year: 2003..The proposed program will bring together experts in chromatin and transcriptional regulation to focus on the intersection between these two areas. ..
