Structure of histone deacetylase complex Rpd3S bound to nucleosome.
Journal
Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
21
06
2023
accepted:
08
09
2023
pubmed:
6
10
2023
medline:
6
10
2023
entrez:
5
10
2023
Statut:
ppublish
Résumé
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 Å 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.
Identifiants
pubmed: 37798513
doi: 10.1038/s41594-023-01121-5
pii: 10.1038/s41594-023-01121-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1893-1901Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
Références
Jenuwein, T. & Allis, C. D. Translating the histone code. Science 293, 1074–1080 (2001).
doi: 10.1126/science.1063127
pubmed: 11498575
Kouzarides, T. Chromatin modifications and their function. Cell 128, 693–705 (2007).
doi: 10.1016/j.cell.2007.02.005
pubmed: 17320507
Li, B., Carey, M. & Workman, J. L. The role of chromatin during transcription. Cell 128, 707–719 (2007).
doi: 10.1016/j.cell.2007.01.015
pubmed: 17320508
Bannister, A. J. & Kouzarides, T. Regulation of chromatin by histone modifications. Cell Res. 21, 381–395 (2011).
doi: 10.1038/cr.2011.22
pubmed: 21321607
pmcid: 3193420
Kornberg, R. D. & Thomas, J. O. Chromatin structure; oligomers of the histones. Science 184, 865–868 (1974).
doi: 10.1126/science.184.4139.865
pubmed: 4825888
Shahbazian, M. D. & Grunstein, M. Functions of site-specific histone acetylation and deacetylation. Annu. Rev. Biochem. 76, 75–100 (2007).
doi: 10.1146/annurev.biochem.76.052705.162114
pubmed: 17362198
Keogh, M. C. et al. Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex. Cell 123, 593–605 (2005).
doi: 10.1016/j.cell.2005.10.025
pubmed: 16286008
Carrozza, M. J. et al. Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell 123, 581–592 (2005).
doi: 10.1016/j.cell.2005.10.023
pubmed: 16286007
Joshi, A. A. & Struhl, K. Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation. Mol. Cell 20, 971–978 (2005).
doi: 10.1016/j.molcel.2005.11.021
pubmed: 16364921
Li, B. et al. Combined action of PHD and chromo domains directs the Rpd3S HDAC to transcribed chromatin. Science 316, 1050–1054 (2007).
doi: 10.1126/science.1139004
pubmed: 17510366
McDaniel, S. L. et al. Combinatorial histone readout by the dual plant homeodomain (PHD) fingers of Rco1 mediates Rpd3S chromatin recruitment and the maintenance of transcriptional fidelity. J. Biol. Chem. 291, 14796–14802 (2016).
doi: 10.1074/jbc.M116.720193
pubmed: 27226578
pmcid: 4938196
Ruan, C., Cui, H., Lee, C. H., Li, S. & Li, B. Homodimeric PHD domain-containing Rco1 subunit constitutes a critical interaction hub within the Rpd3S histone deacetylase complex. J. Biol. Chem. 291, 5428–5438 (2016).
doi: 10.1074/jbc.M115.703637
pubmed: 26747610
pmcid: 4777872
Huh, J. W. et al. Multivalent di-nucleosome recognition enables the Rpd3S histone deacetylase complex to tolerate decreased H3K36 methylation levels. EMBO J. 31, 3564–3574 (2012).
doi: 10.1038/emboj.2012.221
pubmed: 22863776
pmcid: 3433781
Lee, C. H., Wu, J. & Li, B. Chromatin remodelers fine-tune H3K36me-directed deacetylation of neighbor nucleosomes by Rpd3S. Mol. Cell 52, 255–263 (2013).
doi: 10.1016/j.molcel.2013.08.024
pubmed: 24055344
Ruan, C., Lee, C. H., Cui, H., Li, S. & Li, B. Nucleosome contact triggers conformational changes of Rpd3S driving high-affinity H3K36me nucleosome engagement. Cell Rep. 10, 204–215 (2015).
doi: 10.1016/j.celrep.2014.12.027
pubmed: 25578729
pmcid: 4359074
Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).
doi: 10.1038/s41586-021-03819-2
pubmed: 34265844
pmcid: 8371605
Clark, M. D. et al. Structural insights into the assembly of the histone deacetylase-associated Sin3L/Rpd3L corepressor complex. Proc. Natl Acad. Sci. USA 112, E3669–E3678 (2015).
doi: 10.1073/pnas.1504021112
pubmed: 26124119
pmcid: 4507224
Xie, T. et al. Structure of the 30-kDa Sin3-associated protein (SAP30) in complex with the mammalian Sin3A corepressor and its role in nucleic acid binding. J. Biol. Chem. 286, 27814–27824 (2011).
doi: 10.1074/jbc.M111.252494
pubmed: 21676866
pmcid: 3149371
Watson, P. J., Fairall, L., Santos, G. M. & Schwabe, J. W. Structure of HDAC3 bound to co-repressor and inositol tetraphosphate. Nature 481, 335–340 (2012).
doi: 10.1038/nature10728
pubmed: 22230954
pmcid: 3272448
Vannini, A. et al. Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor. Proc. Natl Acad. Sci. USA 101, 15064–15069 (2004).
doi: 10.1073/pnas.0404603101
pubmed: 15477595
pmcid: 524051
Lombardi, P. M., Cole, K. E., Dowling, D. P. & Christianson, D. W. Structure, mechanism, and inhibition of histone deacetylases and related metalloenzymes. Curr. Opin. Struct. Biol. 21, 735–743 (2011).
doi: 10.1016/j.sbi.2011.08.004
pubmed: 21872466
pmcid: 3232309
Watson, P. J. et al. Insights into the activation mechanism of class I HDAC complexes by inositol phosphates. Nat. Commun. 7, 11262 (2016).
Millard, C. J. et al. Class I HDACs share a common mechanism of regulation by inositol phosphates. Mol. Cell 51, 57–67 (2013).
doi: 10.1016/j.molcel.2013.05.020
pubmed: 23791785
pmcid: 3710971
Lee, K. Y., Ranger, M. & Meneghini, M. D. Combinatorial genetic control of Rpd3S through histone H3K4 and H3K36 methylation in budding yeast. G3 (Bethesda) 8, 3411–3420 (2018).
doi: 10.1534/g3.118.200589
pubmed: 30158320
Kumar, G. S. et al. Sequence requirements for combinatorial recognition of histone H3 by the MRG15 and Pf1 subunits of the Rpd3S/Sin3S corepressor complex. J. Mol. Biol. 422, 519–531 (2012).
doi: 10.1016/j.jmb.2012.06.013
pubmed: 22728643
pmcid: 3428507
Wang, H., Farnung, L., Dienemann, C. & Cramer, P. Structure of H3K36-methylated nucleosome-PWWP complex reveals multivalent cross-gyre binding. Nat. Struct. Mol. Biol. 27, 8–13 (2020).
doi: 10.1038/s41594-019-0345-4
pubmed: 31819277
Zhou, K., Gaullier, G. & Luger, K. Nucleosome structure and dynamics are coming of age. Nat. Struct. Mol. Biol. 26, 3–13 (2019).
doi: 10.1038/s41594-018-0166-x
pubmed: 30532059
Govind, C. K. et al. Phosphorylated Pol II CTD recruits multiple HDACs, including Rpd3C(S), for methylation-dependent deacetylation of ORF nucleosomes. Mol. Cell 39, 234–246 (2010).
doi: 10.1016/j.molcel.2010.07.003
pubmed: 20670892
pmcid: 2937259
Yang, X. J. & Seto, E. The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men. Nat. Rev. Mol. Cell Biol. 9, 206–218 (2008).
doi: 10.1038/nrm2346
pubmed: 18292778
pmcid: 2667380
Tough, D. F., Tak, P. P., Tarakhovsky, A. & Prinjha, R. K. Epigenetic drug discovery: breaking through the immune barrier. Nat. Rev. Drug Discov. 15, 835–853 (2016).
doi: 10.1038/nrd.2016.185
pubmed: 27765940
Dyer, P. N. et al. Reconstitution of nucleosome core particles from recombinant histones and DNA. Methods Enzymol. 375, 23–44 (2004).
doi: 10.1016/S0076-6879(03)75002-2
pubmed: 14870657
Wang, H. et al. Structure of the transcription coactivator SAGA. Nature 577, 717–720 (2020).
doi: 10.1038/s41586-020-1933-5
pubmed: 31969703
pmcid: 6994259
Tegunov, D. & Cramer, P. Real-time cryo-electron microscopy data preprocessing with Warp. Nat. Methods 16, 1146–1152 (2019).
doi: 10.1038/s41592-019-0580-y
pubmed: 31591575
pmcid: 6858868
Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife https://doi.org/10.7554/eLife.42166 (2018).
Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).
doi: 10.1038/nmeth.4169
pubmed: 28165473
Varadi, M. et al. AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Res. 50, D439–D444 (2022).
doi: 10.1093/nar/gkab1061
pubmed: 34791371
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486–501 (2010).
Wang, H., Xiong, L. & Cramer, P. Structures and implications of TBP-nucleosome complexes. Proc. Natl Acad. Sci. USA 118, e2108859118 (2021).
Pettersen, E. F. et al. UCSF Chimera–a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).
doi: 10.1002/jcc.20084
pubmed: 15264254
Afonine, P. V. et al. Real-space refinement in PHENIX for cryo-EM and crystallography. Acta Crystallogr. D 74, 531–544 (2018).
Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D 66, 12–21 (2010).
Pettersen, E. F. et al. UCSF ChimeraX: Structure visualization for researchers, educators, and developers. Protein Sci. 30, 70–82 (2021).
doi: 10.1002/pro.3943
pubmed: 32881101