Gary Felsenfeld

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. ncbi request reprint Controlling the double helix
    Gary Felsenfeld
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 5, Room 212, Bethesda, Maryland 20892 0540, USA
    Nature 421:448-53. 2003
  2. ncbi request reprint Critical DNA binding interactions of the insulator protein CTCF: a small number of zinc fingers mediate strong binding, and a single finger-DNA interaction controls binding at imprinted loci
    Mario Renda
    Dipartimento di Scienze Ambientali, Seconda Università degli Studi di Napoli via Vivaldi 43, 81100 Caserta, Italy
    J Biol Chem 282:33336-45. 2007
  3. ncbi request reprint Quantitative approaches to problems of eukaryotic gene expression
    Gary Felsenfeld
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0540, USA
    Biophys Chem 100:607-13. 2003
  4. pmc Silencing of transgene transcription precedes methylation of promoter DNA and histone H3 lysine 9
    Vesco Mutskov
    Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD, USA
    EMBO J 23:138-49. 2004
  5. ncbi request reprint Recruitment of histone modifications by USF proteins at a vertebrate barrier element
    Adam G West
    Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell 16:453-63. 2004
  6. pmc USF1 recruits histone modification complexes and is critical for maintenance of a chromatin barrier
    Suming Huang
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0540, USA
    Mol Cell Biol 27:7991-8002. 2007
  7. ncbi request reprint CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species
    Timur M Yusufzai
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell 13:291-8. 2004
  8. pmc Specific sites in the C terminus of CTCF interact with the SA2 subunit of the cohesin complex and are required for cohesin-dependent insulation activity
    Tiaojiang Xiao
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell Biol 31:2174-83. 2011
  9. pmc Chromatin domains, insulators, and the regulation of gene expression
    Rodolfo Ghirlando
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Key Diseases, National Insitute of Health, 9000 Rockville Pike, Bethesda, MD 20892 0540, USA
    Biochim Biophys Acta 1819:644-51. 2012
  10. pmc The 5'-HS4 chicken beta-globin insulator is a CTCF-dependent nuclear matrix-associated element
    Timur M Yusufzai
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0540, USA
    Proc Natl Acad Sci U S A 101:8620-4. 2004

Collaborators

Detail Information

Publications42

  1. ncbi request reprint Controlling the double helix
    Gary Felsenfeld
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 5, Room 212, Bethesda, Maryland 20892 0540, USA
    Nature 421:448-53. 2003
    ..Chromatin structure is dynamic and exerts profound control over gene expression and other fundamental cellular processes. Changes in its structure can be inherited by the next generation, independent of the DNA sequence itself...
  2. ncbi request reprint Critical DNA binding interactions of the insulator protein CTCF: a small number of zinc fingers mediate strong binding, and a single finger-DNA interaction controls binding at imprinted loci
    Mario Renda
    Dipartimento di Scienze Ambientali, Seconda Università degli Studi di Napoli via Vivaldi 43, 81100 Caserta, Italy
    J Biol Chem 282:33336-45. 2007
    ..This single interaction appears to be critical for allele-specific binding and insulation by CTCF...
  3. ncbi request reprint Quantitative approaches to problems of eukaryotic gene expression
    Gary Felsenfeld
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0540, USA
    Biophys Chem 100:607-13. 2003
    ..We have extended such studies to examine interactions with DNA packaged as chromatin, and to studies of chromatin structure and function at higher levels of organization...
  4. pmc Silencing of transgene transcription precedes methylation of promoter DNA and histone H3 lysine 9
    Vesco Mutskov
    Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD, USA
    EMBO J 23:138-49. 2004
    ..We show that the kinetics of silencing exclude histone H3 K9 and promoter DNA methylation as the primary causative events in our transgene system...
  5. ncbi request reprint Recruitment of histone modifications by USF proteins at a vertebrate barrier element
    Adam G West
    Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell 16:453-63. 2004
    ..We propose that barrier activity requires the constitutive recruitment of H3K4 methylation and histone acetylation at multiple residues to counteract the propagation of condensed chromatin structures...
  6. pmc USF1 recruits histone modification complexes and is critical for maintenance of a chromatin barrier
    Suming Huang
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0540, USA
    Mol Cell Biol 27:7991-8002. 2007
    ..These results show that USF1 plays a direct role in maintaining the barrier, supporting a model in which the insulator works as a barrier by maintaining a local environment of active chromatin...
  7. ncbi request reprint CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species
    Timur M Yusufzai
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell 13:291-8. 2004
    ..These interactions, quite different from those of the gypsy insulator element in Drosophila, may generate similar loop structures, suggesting a common theme and model for enhancer-blocking insulator action...
  8. pmc Specific sites in the C terminus of CTCF interact with the SA2 subunit of the cohesin complex and are required for cohesin-dependent insulation activity
    Tiaojiang Xiao
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell Biol 31:2174-83. 2011
    ..The only direct interaction between CTCF and cohesin involves contact with SA2, which is external to the cohesin ring. This suggests that in recruiting cohesin to CTCF, SA2 could bind first and the ring could assemble subsequently...
  9. pmc Chromatin domains, insulators, and the regulation of gene expression
    Rodolfo Ghirlando
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Key Diseases, National Insitute of Health, 9000 Rockville Pike, Bethesda, MD 20892 0540, USA
    Biochim Biophys Acta 1819:644-51. 2012
    ..This article is part of a Special Issue entitled: Chromatin in time and space...
  10. pmc The 5'-HS4 chicken beta-globin insulator is a CTCF-dependent nuclear matrix-associated element
    Timur M Yusufzai
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0540, USA
    Proc Natl Acad Sci U S A 101:8620-4. 2004
    ....
  11. pmc Epigenetic control of the variable expression of a Plasmodium falciparum receptor protein for erythrocyte invasion
    Lubin Jiang
    Laboratory of Malaria Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
    Proc Natl Acad Sci U S A 107:2224-9. 2010
    ..Our data indicate that the failure of Dd2 to express the sialic acid-independent invasion receptor gene RH4 is associated with the epigenetic silencing mark H3K9 trimethylation present throughout the cycle...
  12. pmc Methylation of histone H4 by arginine methyltransferase PRMT1 is essential in vivo for many subsequent histone modifications
    Suming Huang
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0540, USA
    Genes Dev 19:1885-93. 2005
    ..Consistent with earlier reports of experiments in vitro, H4 Arg3 methylation by PRMT1 appears to be essential in vivo for the establishment or maintenance of a wide range of "active" chromatin modifications...
  13. pmc Maintenance of a constitutive heterochromatin domain in vertebrates by a Dicer-dependent mechanism
    Keith E Giles
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0540, USA
    Nat Cell Biol 12:94-9; sup pp 1-6. 2010
    ..Heterochromatic domains of this kind, which are widely distributed in vertebrate genomes, thus seem to be maintained in their condensed form by highly conserved mechanisms...
  14. pmc Vezf1 protein binding sites genome-wide are associated with pausing of elongating RNA polymerase II
    Humaira Gowher
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0540, USA
    Proc Natl Acad Sci U S A 109:2370-5. 2012
    ..We further show that Vezf1 interacts with Mrg15/Mrgbp, a protein that recognizes H3K36 trimethylation, consistent with the role of histone modifications at alternatively spliced sites...
  15. doi request reprint Mapping of INS promoter interactions reveals its role in long-range regulation of SYT8 transcription
    Zhixiong Xu
    National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
    Nat Struct Mol Biol 18:372-8. 2011
    ..This suggests a function for the INS promoter in coordinating insulin transcription and secretion through long-range regulation of SYT8 expression in human islets...
  16. pmc Mediation of CTCF transcriptional insulation by DEAD-box RNA-binding protein p68 and steroid receptor RNA activator SRA
    Hongjie Yao
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Genes Dev 24:2543-55. 2010
    ..The results suggest that p68/SRA stabilizes the interaction of cohesin with CTCF by binding to both, and is required for proper insulator function...
  17. pmc The barrier function of an insulator couples high histone acetylation levels with specific protection of promoter DNA from methylation
    Vesco J Mutskov
    Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA
    Genes Dev 16:1540-54. 2002
    ..We suggest that this acetylation is in turn responsible for the maintenance of a region of unmethylated DNA over the promoter. Whereas DNA methylation often leads to histone deacetylation, here acetylation appears to prevent methylation...
  18. ncbi request reprint The human insulin gene displays transcriptionally active epigenetic marks in islet-derived mesenchymal precursor cells in the absence of insulin expression
    Vesco Mutskov
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Stem Cells 25:3223-33. 2007
    ..This epigenetic signature may be a general mechanism whereby tissue-derived precursor cells are committed to a distinct specification. Disclosure of potential conflicts of interest is found at the end of this article...
  19. pmc Position-effect protection and enhancer blocking by the chicken beta-globin insulator are separable activities
    Felix Recillas-Targa
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0540, USA
    Proc Natl Acad Sci U S A 99:6883-8. 2002
    ....
  20. ncbi request reprint Both CTCF-dependent and -independent insulators are found between the mouse T cell receptor alpha and Dad1 genes
    Frédérique Magdinier
    Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 0504, USA
    J Biol Chem 279:25381-9. 2004
    ..However, other regions within the 6-kb element that also can block enhancers clearly do not harbor CTCF sites and thus must reflect the presence of a previously undetected and distinct vertebrate insulator activity...
  21. pmc Hydrodynamic studies on defined heterochromatin fragments support a 30-nm fiber having six nucleosomes per turn
    Rodolfo Ghirlando
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA
    J Mol Biol 376:1417-25. 2008
    ....
  22. pmc We gather together: insulators and genome organization
    Julie A Wallace
    Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892 0540, United States
    Curr Opin Genet Dev 17:400-7. 2007
    ..The properties of CTCF, and its newly described genomic distribution, suggest that it may play an important role in large-scale nuclear architecture, perhaps mediated by the co-factors with which it interacts in vivo...
  23. pmc H3.3/H2A.Z double variant-containing nucleosomes mark 'nucleosome-free regions' of active promoters and other regulatory regions
    Chunyuan Jin
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
    Nat Genet 41:941-5. 2009
    ..Other combinations of variants have different distributions, consistent with distinct roles for histone variants in the modulation of gene expression...
  24. pmc The human insulin gene is part of a large open chromatin domain specific for human islets
    Vesco Mutskov
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 106:17419-24. 2009
    ..The presence of islet specific intergenic transcripts suggests their possible function in the maintenance of this unusual large open chromatin domain...
  25. pmc The insulation of genes from external enhancers and silencing chromatin
    Bonnie Burgess-Beusse
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0540, USA
    Proc Natl Acad Sci U S A 99:16433-7. 2002
    ..Insulators thus are complex elements that can help to preserve the independent function of genes embedded in a genome in which they are surrounded by regulatory signals they must ignore...
  26. pmc Nucleosome stability mediated by histone variants H3.3 and H2A.Z
    Chunyuan Jin
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0540, USA
    Genes Dev 21:1519-29. 2007
    ..3 and H2A.Z, and should therefore be extremely sensitive to disruption...
  27. ncbi request reprint Insulators: exploiting transcriptional and epigenetic mechanisms
    Miklos Gaszner
    National Institute of Diabetes and Digestive and Kidney Diseases, National Institues of Health, Bethesda, Maryland 20892 0540, USA
    Nat Rev Genet 7:703-13. 2006
    ..These new insights also suggest that the mechanisms of action of both enhancer blockers and barriers might not be unique to these types of element, but instead are adaptations of other gene-regulatory mechanisms...
  28. pmc Variegated expression from the murine band 3 (AE1) promoter in transgenic mice is associated with mRNA transcript initiation at upstream start sites and can be suppressed by the addition of the chicken beta-globin 5' HS4 insulator element
    Tiffany F Frazar
    Hematopoiesis Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA
    Mol Cell Biol 23:4753-63. 2003
    ..We conclude that the chicken beta-globin 5'HS4 element is necessary for full function of the AE1 promoter and that position effect variegation is associated with RNA transcription from the upstream start sites...
  29. ncbi request reprint Physical properties of a genomic condensed chromatin fragment
    Rodolfo Ghirlando
    Department of Health and Human Services, Laboratory of Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Mol Biol 336:597-605. 2004
    ..The method is generally applicable to homogeneous particles of unique sequence at genomic abundance...
  30. pmc Distribution of histone H3.3 in hematopoietic cell lineages
    Chunyuan Jin
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0540, USA
    Proc Natl Acad Sci U S A 103:574-9. 2006
    ..3 stimulates expression. This finding suggests that these histone variants can be active rather than passive participants in regulation of expression...
  31. pmc Conserved CTCF insulator elements flank the mouse and human beta-globin loci
    Catherine M Farrell
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Cell Biol 22:3820-31. 2002
    ....
  32. pmc High resolution analysis of the chromatin landscape of the IgE switch region in human B cells
    Sandeep Dayal
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 6:e24571. 2011
    ..These data suggest that acetylation and K4 tri-methylation of histone H3 may represent marks of recombinationally active chromatin and further implicates splicing in the regulation of AID action...
  33. pmc Vezf1 regulates genomic DNA methylation through its effects on expression of DNA methyltransferase Dnmt3b
    Humaira Gowher
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Genes Dev 22:2075-84. 2008
    ..These results suggest that naturally occurring mutations in Vezf1/BGP1 might have widespread effects on DNA methylation patterns and therefore on epigenetic regulation of gene expression...
  34. doi request reprint Physical chemistry of nucleic acids and their complexes
    Rodolfo Ghirlando
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892
    Biopolymers 99:910-5. 2013
    ..Published 2013 Wiley Periodicals, Inc*. Biopolymers 99: 910-915, 2013. ..
  35. pmc Chromatin structure outside and inside the nucleus
    Rodolfo Ghirlando
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0540
    Biopolymers 99:225-32. 2013
    ..2012 Wiley Periodicals, Inc. Biopolymers 99: 225-232, 2013...
  36. pmc Order from chaos in the nucleus
    Zhixiong Xu
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell 48:327-8. 2012
    ..2012, in this issue of Molecular Cell) show that it is organized into defined and functionally important domains marked by preferred intradomain physical contacts, and with boundaries associated with insulator protein occupancy...
  37. ncbi request reprint Insulators: many functions, many mechanisms
    Adam G West
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0540, USA
    Genes Dev 16:271-88. 2002
  38. ncbi request reprint Transcription of Ig germline genes in single human B cells and the role of cytokines in isotype determination
    David J Fear
    The Randall Center, King s College London, United Kingdom
    J Immunol 173:4529-38. 2004
    ..We have also found that the levels of germline gene transcription cannot fully account for the levels of secretion of the different Ig isotypes, and that secretion of IgE, in particular, is suppressed relative to that of IgG...
  39. ncbi request reprint Extended core sequences from the cHS4 insulator are necessary for protecting retroviral vectors from silencing position effects
    Mari Aker
    Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA
    Hum Gene Ther 18:333-43. 2007
    ....
  40. ncbi request reprint Antagonism between DNA hypermethylation and enhancer-blocking activity at the H19 DMD is uncovered by CpG mutations
    Nora Engel
    Howard Hughes Medical Institute and Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Nat Genet 36:883-8. 2004
    ..Thus, the nine CpG mutations in the DMD showed that the two parental-specific roles of the H19 DMD, methylation maintenance and insulator assembly, are antagonistic...
  41. pmc Obituary. Robert Simpson
    Gary Felsenfeld
    Nucleic Acids Res 32:2975-6. 2004
  42. ncbi request reprint Chromatin remodeling by RNA polymerases
    Vasily M Studitsky
    Department of Pharmacology, University of Medicine and Dentistry New Jersey, 675 Hoes Lane, Room 405, Piscataway, NJ 08854, USA
    Trends Biochem Sci 29:127-35. 2004
    ..Analysis of the mechanisms of transcription through chromatin should provide important information about mechanisms of chromatin remodeling and gene regulation at the level of transcript elongation...