Home LiteratureArticle Details
PMID: 19379692 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Dimethylation of H3K4 by Set1 recruits the Set3 histone deacetylase complex to 5' transcribed regions.

Cell ·Vol. 137 ·No. 2 ·2009-04-17 ·Pages 259-72

Kim T, Buratowski S

Abstract

Cotranscriptional histone methylations by Set1 and Set2 have been shown to affect histone acetylation at promoters and 3' regions of genes, respectively. While histone H3K4 trimethylation (H3K4me3) is thought to promote nucleosome acetylation and remodeling near promoters, we show here that H3K4 dimethylation (H3K4me2) by Set1 leads to reduced histone acetylation levels near 5' ends of genes. H3K4me2 recruits the Set3 complex via the Set3 PHD finger, localizing the Hos2 and Hst1 subunits to deacetylate histones in 5' transcribed regions. Cells lacking the Set1-Set3 complex pathway are sensitive to mycophenolic acid and have reduced polymerase levels at a Set3 target gene, suggesting a positive role in transcription. We propose that Set1 establishes two distinct chromatin zones on genes: H3K4me3 leads to high levels of acetylation and low nucleosome density at promoters, while H3K4me2 just downstream recruits the Set3 complex to suppress nucleosome acetylation and remodeling.

MeSH Terms
Acetylation Chromatin Assembly and Disassembly DNA-Binding Proteins/metabolism Histone Deacetylases/metabolism Histone-Lysine N-Methyltransferase Histones/metabolism Methylation Nucleosomes/metabolism Saccharomyces cerevisiae/metabolism Saccharomyces cerevisiae Proteins/metabolism Telomere/metabolism Transcription Factors/metabolism Transcription, Genetic
Chemicals
DNA-Binding Proteins Histones Nucleosomes Saccharomyces cerevisiae Proteins Transcription Factors Histone-Lysine N-Methyltransferase SET1 protein, S cerevisiae Set3 protein, S cerevisiae Histone Deacetylases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kim TaeSoo
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Buratowski Stephen
References (59)
59 references, click to expand
  1. Histone H3 Lys 4 methylation: caught in a bind?
    Genes Dev. 2006 Oct 15;20(20):2779-86 PMID: 17043307
  2. Combined action of PHD and chromo domains directs the Rpd3S HDAC to transcribed chromatin.
    Science. 2007 May 18;316(5827):1050-4 PMID: 17510366
  3. Association of the histone methyltransferase Set2 with RNA polymerase II plays a role in transcription elongation.
    J Biol Chem. 2002 Dec 20;277(51):49383-8 PMID: 12381723
  4. Human but not yeast CHD1 binds directly and selectively to histone H3 methylated at lysine 4 via its tandem chromodomains.
    J Biol Chem. 2005 Dec 23;280(51):41789-92 PMID: 16263726
  5. High-resolution profiling of histone methylations in the human genome.
    Cell. 2007 May 18;129(4):823-37 PMID: 17512414
  6. Regulation of histone modification and cryptic transcription by the Bur1 and Paf1 complexes.
    EMBO J. 2007 Nov 14;26(22):4646-56 PMID: 17948059
  7. How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers.
    Nat Struct Mol Biol. 2007 Nov;14(11):1025-1040 PMID: 17984965
  8. Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II.
    Mol Cell Biol. 2003 Jun;23(12):4207-18 PMID: 12773564
  9. Two Saccharomyces cerevisiae JmjC domain proteins demethylate histone H3 Lys36 in transcribed regions to promote elongation.
    J Biol Chem. 2007 Jul 20;282(29):20827-35 PMID: 17525156
  10. The role of chromatin during transcription.
    Cell. 2007 Feb 23;128(4):707-19 PMID: 17320508
  11. Chromatin modifications and their function.
    Cell. 2007 Feb 23;128(4):693-705 PMID: 17320507
  12. Phosphorylation of RNA polymerase II CTD regulates H3 methylation in yeast.
    Genes Dev. 2003 Mar 1;17(5):654-63 PMID: 12629047
  13. Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription.
    Cell. 2005 Nov 18;123(4):581-92 PMID: 16286007
  14. Histone H3 lysine 4 mono-methylation does not require ubiquitination of histone H2B.
    J Mol Biol. 2005 Oct 28;353(3):477-84 PMID: 16185711
  15. Histone H2B ubiquitylation controls processive methylation but not monomethylation by Dot1 and Set1.
    Mol Cell. 2005 Jul 22;19(2):271-7 PMID: 16039595
  16. Genome-wide, as opposed to local, antisilencing is mediated redundantly by the euchromatic factors Set1 and H2A.Z.
    Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16609-14 PMID: 17925448
  17. The requirements for COMPASS and Paf1 in transcriptional silencing and methylation of histone H3 in Saccharomyces cerevisiae.
    Genetics. 2006 Jun;173(2):557-67 PMID: 16582434
  18. Sum1 and Hst1 repress middle sporulation-specific gene expression during mitosis in Saccharomyces cerevisiae.
    EMBO J. 1999 Nov 15;18(22):6448-54 PMID: 10562556
  19. Tandem affinity purification and identification of protein complex components.
    Methods. 2004 Jul;33(3):239-44 PMID: 15157891
  20. Yng1 PHD finger binding to H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs.
    Mol Cell. 2006 Dec 8;24(5):785-796 PMID: 17157260
  21. Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity.
    Mol Cell. 2003 Mar;11(3):709-19 PMID: 12667453
  22. ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression.
    Nature. 2006 Jul 6;442(7098):96-9 PMID: 16728974
  23. Methylation of histone H3 mediates the association of the NuA3 histone acetyltransferase with chromatin.
    Mol Cell Biol. 2006 Apr;26(8):3018-28 PMID: 16581777
  24. Saccharomyces cerevisiae Set1p is a methyltransferase specific for lysine 4 of histone H3 and is required for efficient gene expression.
    Yeast. 2003 Jul 15;20(9):827-35 PMID: 12845608
  25. Chd1 chromodomain links histone H3 methylation with SAGA- and SLIK-dependent acetylation.
    Nature. 2005 Jan 27;433(7024):434-8 PMID: 15647753
  26. The Bur1/Bur2 complex is required for histone H2B monoubiquitination by Rad6/Bre1 and histone methylation by COMPASS.
    Mol Cell. 2005 Nov 23;20(4):589-99 PMID: 16307922
  27. The S. cerevisiae SET3 complex includes two histone deacetylases, Hos2 and Hst1, and is a meiotic-specific repressor of the sporulation gene program.
    Genes Dev. 2001 Nov 15;15(22):2991-3004 PMID: 11711434
  28. Dot1p modulates silencing in yeast by methylation of the nucleosome core.
    Cell. 2002 Jun 14;109(6):745-56 PMID: 12086673
  29. Molecular mechanism of histone H3K4me3 recognition by plant homeodomain of ING2.
    Nature. 2006 Jul 6;442(7098):100-3 PMID: 16728977
  30. Structural polymorphism of chromodomains in Chd1.
    J Mol Biol. 2007 Jan 26;365(4):1047-62 PMID: 17098252
  31. Molecular implications of evolutionary differences in CHD double chromodomains.
    J Mol Biol. 2007 Jun 1;369(2):334-42 PMID: 17433364
  32. Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
    Nature. 2006 Mar 30;440(7084):637-43 PMID: 16554755
  33. Histone crosstalk between H2B monoubiquitination and H3 methylation mediated by COMPASS.
    Cell. 2007 Dec 14;131(6):1084-96 PMID: 18083099
  34. Global loss of Set1-mediated H3 Lys4 trimethylation is associated with silencing defects in Saccharomyces cerevisiae.
    J Biol Chem. 2005 Aug 5;280(31):28761-5 PMID: 15964832
  35. The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men.
    Nat Rev Mol Cell Biol. 2008 Mar;9(3):206-18 PMID: 18292778
  36. Toward a comprehensive atlas of the physical interactome of Saccharomyces cerevisiae.
    Mol Cell Proteomics. 2007 Mar;6(3):439-50 PMID: 17200106
  37. The histone 3 lysine 36 methyltransferase, SET2, is involved in transcriptional elongation.
    Nucleic Acids Res. 2003 May 15;31(10):2475-82 PMID: 12736296
  38. Molecular basis for site-specific read-out of histone H3K4me3 by the BPTF PHD finger of NURF.
    Nature. 2006 Jul 6;442(7098):91-5 PMID: 16728978
  39. Genome-wide histone modifications: gaining specificity by preventing promiscuity.
    Curr Opin Cell Biol. 2002 Dec;14(6):756-62 PMID: 12473351
  40. Infrequently transcribed long genes depend on the Set2/Rpd3S pathway for accurate transcription.
    Genes Dev. 2007 Jun 1;21(11):1422-30 PMID: 17545470
  41. Methylation of H3 lysine 4 at euchromatin promotes Sir3p association with heterochromatin.
    J Biol Chem. 2004 Nov 12;279(46):47506-12 PMID: 15280381
  42. Eaf3 regulates the global pattern of histone acetylation in Saccharomyces cerevisiae.
    Mol Cell Biol. 2004 Jan;24(2):757-64 PMID: 14701747
  43. Set2 is a nucleosomal histone H3-selective methyltransferase that mediates transcriptional repression.
    Mol Cell Biol. 2002 Mar;22(5):1298-306 PMID: 11839797
  44. MLL5, a homolog of Drosophila trithorax located within a segment of chromosome band 7q22 implicated in myeloid leukemia.
    Oncogene. 2002 Jul 18;21(31):4849-54 PMID: 12101424
  45. Histone trimethylation by Set1 is coordinated by the RRM, autoinhibitory, and catalytic domains.
    EMBO J. 2005 Mar 23;24(6):1222-31 PMID: 15775977
  46. A novel domain in Set2 mediates RNA polymerase II interaction and couples histone H3 K36 methylation with transcript elongation.
    Mol Cell Biol. 2005 Apr;25(8):3305-16 PMID: 15798214
  47. Hos2p/Set3p deacetylase complex signals secretory stress through the Mpk1p cell integrity pathway.
    Eukaryot Cell. 2008 Jul;7(7):1191-9 PMID: 18487345
  48. Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex.
    Cell. 2005 Nov 18;123(4):593-605 PMID: 16286008
  49. Requirement of Hos2 histone deacetylase for gene activity in yeast.
    Science. 2002 Nov 15;298(5597):1412-4 PMID: 12434058
  50. The multiple faces of Set1.
    Biochem Cell Biol. 2006 Aug;84(4):536-48 PMID: 16936826
  51. Single-nucleosome mapping of histone modifications in S. cerevisiae.
    PLoS Biol. 2005 Oct;3(10):e328 PMID: 16122352
  52. Proteome-wide analysis in Saccharomyces cerevisiae identifies several PHD fingers as novel direct and selective binding modules of histone H3 methylated at either lysine 4 or lysine 36.
    J Biol Chem. 2007 Jan 26;282(4):2450-5 PMID: 17142463
  53. Genomic maps and comparative analysis of histone modifications in human and mouse.
    Cell. 2005 Jan 28;120(2):169-81 PMID: 15680324
  54. Dynamic lysine methylation on histone H3 defines the regulatory phase of gene transcription.
    Mol Cell. 2005 Jun 10;18(6):723-34 PMID: 15949446
  55. Genome-wide map of nucleosome acetylation and methylation in yeast.
    Cell. 2005 Aug 26;122(4):517-27 PMID: 16122420
  56. BUR kinase selectively regulates H3 K4 trimethylation and H2B ubiquitylation through recruitment of the PAF elongation complex.
    Curr Biol. 2005 Aug 23;15(16):1487-93 PMID: 16040246
  57. Poised RNA polymerase II gives pause for thought.
    Cell. 2008 May 16;133(4):581-4 PMID: 18485867
  58. Recognition of histone H3 lysine-4 methylation by the double tudor domain of JMJD2A.
    Science. 2006 May 5;312(5774):748-51 PMID: 16601153
  59. A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling.
    Nature. 2006 Jul 6;442(7098):86-90 PMID: 16728976
Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2009.02.045
Published
2009-04-17
Pages
259-72
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2802783
Subset
IM
Grants
NIGMS NIH HHS · R01 GM046498 · United States
NIGMS NIH HHS · R01 GM046498-17 · United States
NIGMS NIH HHS · R01 GM046498-18 · United States
NIGMS NIH HHS · GM46498 · United States
External Links
PubMed source DOI: 10.1016/j.cell.2009.02.045 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2