| Structural highlights
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
Acetylation of histones is a key post-translational modification that guides gene expression regulation. In yeast, the class I histone deacetylase containing Rpd3S complex plays a critical role in the suppression of spurious transcription by removing histone acetylation from actively transcribed genes. The S. cerevisiae Rpd3S complex has five subunits (Rpd3, Sin3, Rco1, Eaf3, and Ume1) but its subunit stoichiometry and how the complex engages nucleosomes to achieve substrate specificity remains elusive. Here we report the cryo-EM structure of the complete Rpd3S complex bound to a nucleosome. Sin3 and two copies of subunits Rco1 and Eaf3 encircle the deacetylase subunit Rpd3 and coordinate the positioning of Ume1. The Rpd3S complex binds both trimethylated H3 tails at position lysine 36 and makes multiple additional contacts with the nucleosomal DNA and the H2A-H2B acidic patch. Direct regulation via the Sin3 subunit coordinates binding of the acetylated histone substrate to achieve substrate specificity.
Structure of the complete Saccharomyces cerevisiae Rpd3S-nucleosome complex.,Markert JW, Vos SM, Farnung L Nat Commun. 2023 Dec 8;14(1):8128. doi: 10.1038/s41467-023-43968-8. PMID:38065958[19]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Markert JW, Vos SM, Farnung L. Structure of the complete Saccharomyces cerevisiae Rpd3S-nucleosome complex. Nat Commun. 2023 Dec 8;14(1):8128. PMID:38065958 doi:10.1038/s41467-023-43968-8
|
