Proteopedia

8hxx

Cryo-EM structure of the histone deacetylase complex Rpd3SCryo-EM structure of the histone deacetylase complex Rpd3S

Structural highlights

8hxx is a 7 chain structure with sequence from Saccharomyces cerevisiae and Xenopus laevis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SIN3_YEAST Catalytic component of the RPD3 histone deacetylase complexes RPD3C(L) and RPD3C(S) responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. SIN3 has also a RPD3 independent function required for normal longevity.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18]

Publication Abstract from PubMed

Crosstalk between histone modifications represents a fundamental epigenetic mechanism in gene regulation. During the transcription elongation process, the histone deacetylase complex Rpd3S is recruited to H3K36-methylated nucleosomes to suppress cryptic transcription initiation. However, how subunits of Rpd3S are assembled and coordinated to recognize nucleosomal substrates and exert their deacetylation function remains unclear. Here we report the structure of Saccharomyces cerevisiae Rpd3S deacetylase bound to H3K36me3-modified nucleosome at 3.1 A resolution. It shows that Sin3 and Rco1 subunits orchestrate the assembly of the complex and mediate its contact with nucleosome at multiple sites, with the Sin3-DNA interface as a pivotal anchor. The PHD1 domain of Rco1 recognizes the unmodified H3K4 and places the following H3 tail toward the active site of Rpd3, while the chromodomain of Eaf3 subunit recognizes the H3K36me3 mark and contacts both nucleosomal and linker DNA. The second copy of Eaf3-Rco1 is involved in neighboring nucleosome binding. Our work unravels the structural basis of chromatin targeting and deacetylation by the Rpd3S complex.

Structure of histone deacetylase complex Rpd3S bound to nucleosome.,Li W, Cui H, Lu Z, Wang H Nat Struct Mol Biol. 2023 Dec;30(12):1893-1901. doi: 10.1038/s41594-023-01121-5. , Epub 2023 Oct 5. PMID:37798513[19]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Sun ZW, Hampsey M. A general requirement for the Sin3-Rpd3 histone deacetylase complex in regulating silencing in Saccharomyces cerevisiae. Genetics. 1999 Jul;152(3):921-32. PMID:10388812 doi:10.1093/genetics/152.3.921
  2. ↑ Elkhaimi M, Kaadige MR, Kamath D, Jackson JC, Biliran H Jr, Lopes JM. Combinatorial regulation of phospholipid biosynthetic gene expression by the UME6, SIN3 and RPD3 genes. Nucleic Acids Res. 2000 Aug 15;28(16):3160-7. PMID:10931932 doi:10.1093/nar/28.16.3160
  3. ↑ Washburn BK, Esposito RE. Identification of the Sin3-binding site in Ume6 defines a two-step process for conversion of Ume6 from a transcriptional repressor to an activator in yeast. Mol Cell Biol. 2001 Mar;21(6):2057-69. PMID:11238941 doi:10.1128/MCB.21.6.2057-2069.2001
  4. ↑ Scott KL, Plon SE. Loss of Sin3/Rpd3 histone deacetylase restores the DNA damage response in checkpoint-deficient strains of Saccharomyces cerevisiae. Mol Cell Biol. 2003 Jul;23(13):4522-31. PMID:12808094 doi:10.1128/MCB.23.13.4522-4531.2003
  5. ↑ Jazayeri A, McAinsh AD, Jackson SP. Saccharomyces cerevisiae Sin3p facilitates DNA double-strand break repair. Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1644-9. PMID:14711989 doi:10.1073/pnas.0304797101
  6. ↑ De Nadal E, Zapater M, Alepuz PM, Sumoy L, Mas G, Posas F. The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes. Nature. 2004 Jan 22;427(6972):370-4. PMID:14737171 doi:10.1038/nature02258
  7. ↑ Schröder M, Clark R, Liu CY, Kaufman RJ. The unfolded protein response represses differentiation through the RPD3-SIN3 histone deacetylase. EMBO J. 2004 Jun 2;23(11):2281-92. PMID:15141165 doi:10.1038/sj.emboj.7600233
  8. ↑ Aparicio JG, Viggiani CJ, Gibson DG, Aparicio OM. The Rpd3-Sin3 histone deacetylase regulates replication timing and enables intra-S origin control in Saccharomyces cerevisiae. Mol Cell Biol. 2004 Jun;24(11):4769-80. PMID:15143171 doi:10.1128/MCB.24.11.4769-4780.2004
  9. ↑ Kaeberlein M, Kirkland KT, Fields S, Kennedy BK. Genes determining yeast replicative life span in a long-lived genetic background. Mech Ageing Dev. 2005 Apr;126(4):491-504. PMID:15722108 doi:10.1016/j.mad.2004.10.007
  10. ↑ Yoshimoto H, Ohmae M, Yamashita I. The Saccharomyces cerevisiae GAM2/SIN3 protein plays a role in both activation and repression of transcription. Mol Gen Genet. 1992 May;233(1-2):327-30. PMID:1603074 doi:10.1007/BF00587597
  11. ↑ Keogh MC, Kurdistani SK, Morris SA, Ahn SH, Podolny V, Collins SR, Schuldiner M, Chin K, Punna T, Thompson NJ, Boone C, Emili A, Weissman JS, Hughes TR, Strahl BD, Grunstein M, Greenblatt JF, Buratowski S, Krogan NJ. Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex. Cell. 2005 Nov 18;123(4):593-605. PMID:16286008 doi:10.1016/j.cell.2005.10.025
  12. ↑ Vidal M, Strich R, Esposito RE, Gaber RF. RPD1 (SIN3/UME4) is required for maximal activation and repression of diverse yeast genes. Mol Cell Biol. 1991 Dec;11(12):6306-16. PMID:1944290 doi:10.1128/mcb.11.12.6306-6316.1991
  13. ↑ Wang H, Clark I, Nicholson PR, Herskowitz I, Stillman DJ. The Saccharomyces cerevisiae SIN3 gene, a negative regulator of HO, contains four paired amphipathic helix motifs. Mol Cell Biol. 1990 Nov;10(11):5927-36. PMID:2233725 doi:10.1128/mcb.10.11.5927-5936.1990
  14. ↑ Wang H, Stillman DJ. Transcriptional repression in Saccharomyces cerevisiae by a SIN3-LexA fusion protein. Mol Cell Biol. 1993 Mar;13(3):1805-14. PMID:8441414 doi:10.1128/mcb.13.3.1805-1814.1993
  15. ↑ Vannier D, Balderes D, Shore D. Evidence that the transcriptional regulators SIN3 and RPD3, and a novel gene (SDS3) with similar functions, are involved in transcriptional silencing in S. cerevisiae. Genetics. 1996 Dec;144(4):1343-53. PMID:8978024 doi:10.1093/genetics/144.4.1343
  16. ↑ Kasten MM, Dorland S, Stillman DJ. A large protein complex containing the yeast Sin3p and Rpd3p transcriptional regulators. Mol Cell Biol. 1997 Aug;17(8):4852-8. PMID:9234741 doi:10.1128/MCB.17.8.4852
  17. ↑ Rundlett SE, Carmen AA, Suka N, Turner BM, Grunstein M. Transcriptional repression by UME6 involves deacetylation of lysine 5 of histone H4 by RPD3. Nature. 1998 Apr 23;392(6678):831-5. PMID:9572144 doi:10.1038/33952
  18. ↑ Kadosh D, Struhl K. Targeted recruitment of the Sin3-Rpd3 histone deacetylase complex generates a highly localized domain of repressed chromatin in vivo. Mol Cell Biol. 1998 Sep;18(9):5121-7. PMID:9710596 doi:10.1128/MCB.18.9.5121
  19. ↑ Li W, Cui H, Lu Z, Wang H. Structure of histone deacetylase complex Rpd3S bound to nucleosome. Nat Struct Mol Biol. 2023 Dec;30(12):1893-1901. PMID:37798513 doi:10.1038/s41594-023-01121-5

8hxx, resolution 3.00Å

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