The RPD3L Deacetylation Complex is Required for Facultative Heterochromatin Repression in

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2024 Jul 29

PMID 39074265

Authors

Colleen C Mumford

Hideki Tanizawa

Elizabeth T Wiles

Kevin J McNaught

Kirsty Jamieson

Kenta Tsukamoto

Eric U Selker

Affiliations

Soon will be listed here.

Abstract

Repression of facultative heterochromatin is essential for developmental processes in numerous organisms. Methylation of histone H3 lysine 27 (H3K27) by Polycomb repressive complex 2 is a prominent feature of facultative heterochromatin in both fungi and higher eukaryotes. Although this methylation is frequently associated with silencing, the detailed mechanism of repression remains incompletely understood. We utilized a forward genetics approach to identify genes required to maintain silencing at facultative heterochromatin genes in and identified three previously uncharacterized genes that are important for silencing: (), (; ), and (; ). We found that SDS3, RLP1, and RLP2 associate with homologs of the Rpd3L complex and are required for repression of a subset of H3K27-methylated genes. Deletion of these genes does not lead to loss of H3K27 methylation but increases acetylation of histone H3 lysine 14 at up-regulated genes, suggesting that RPD3L-driven deacetylation is a factor required for silencing of facultative heterochromatin in a, and perhaps in other organisms.

Citing Articles

Histone deacetylase-1 is required for epigenome stability in .

Ebot-Ojong F, Ferraro A, Kaddar F, Hull-Crew C, Scadden A, Klocko A bioRxiv. 2025; .

PMID: 39896537 PMC: 11785058. DOI: 10.1101/2025.01.17.633486.

The RPD3L deacetylation complex is required for facultative heterochromatin repression in .

Mumford C, Tanizawa H, Wiles E, McNaught K, Jamieson K, Tsukamoto K Proc Natl Acad Sci U S A. 2024; 121(32):e2404770121.

PMID: 39074265 PMC: 11317574. DOI: 10.1073/pnas.2404770121.

References

Zhang Y, Wang L, Liang S, Zhang P, Kang R, Zhang M . FpDep1, a component of Rpd3L histone deacetylase complex, is important for vegetative development, ROS accumulation, and pathogenesis in Fusarium pseudograminearum. Fungal Genet Biol. 2019; 135:103299. DOI: 10.1016/j.fgb.2019.103299. View

Pomraning K, Smith K, Freitag M . Bulk segregant analysis followed by high-throughput sequencing reveals the Neurospora cell cycle gene, ndc-1, to be allelic with the gene for ornithine decarboxylase, spe-1. Eukaryot Cell. 2011; 10(6):724-33. PMC: 3127673. DOI: 10.1128/EC.00016-11. View

Tie F, Banerjee R, Saiakhova A, Howard B, Monteith K, Scacheri P . Trithorax monomethylates histone H3K4 and interacts directly with CBP to promote H3K27 acetylation and antagonize Polycomb silencing. Development. 2014; 141(5):1129-39. PMC: 3929413. DOI: 10.1242/dev.102392. View

Otte A, Kwaks T . Gene repression by Polycomb group protein complexes: a distinct complex for every occasion?. Curr Opin Genet Dev. 2003; 13(5):448-54. DOI: 10.1016/s0959-437x(03)00108-4. View

Holoch D, Margueron R . Mechanisms Regulating PRC2 Recruitment and Enzymatic Activity. Trends Biochem Sci. 2017; 42(7):531-542. DOI: 10.1016/j.tibs.2017.04.003. View

Wiles E, McNaught K, Kaur G, Selker J, Ormsby T, Aravind L . Evolutionarily ancient BAH-PHD protein mediates Polycomb silencing. Proc Natl Acad Sci U S A. 2020; 117(21):11614-11623. PMC: 7261115. DOI: 10.1073/pnas.1918776117. View

Kouzarides T . Chromatin modifications and their function. Cell. 2007; 128(4):693-705. DOI: 10.1016/j.cell.2007.02.005. View

Carrozza M, Florens L, Swanson S, Shia W, Anderson S, Yates J . Stable incorporation of sequence specific repressors Ash1 and Ume6 into the Rpd3L complex. Biochim Biophys Acta. 2005; 1731(2):77-87. DOI: 10.1016/j.bbaexp.2005.09.005. View

Ridenour J, Moller M, Freitag M . Polycomb Repression without Bristles: Facultative Heterochromatin and Genome Stability in Fungi. Genes (Basel). 2020; 11(6). PMC: 7348808. DOI: 10.3390/genes11060638. View

10.

Carrozza M, Li B, Florens L, Suganuma T, Swanson S, Lee K . Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell. 2005; 123(4):581-92. DOI: 10.1016/j.cell.2005.10.023. View

11.

Clark M, Marcum R, Graveline R, Chan C, Xie T, Chen Z . Structural insights into the assembly of the histone deacetylase-associated Sin3L/Rpd3L corepressor complex. Proc Natl Acad Sci U S A. 2015; 112(28):E3669-78. PMC: 4507224. DOI: 10.1073/pnas.1504021112. View

12.

Mumford C, Tanizawa H, Wiles E, McNaught K, Jamieson K, Tsukamoto K . The RPD3L deacetylation complex is required for facultative heterochromatin repression in . Proc Natl Acad Sci U S A. 2024; 121(32):e2404770121. PMC: 11317574. DOI: 10.1073/pnas.2404770121. View

13.

Kurdistani S, Robyr D, Tavazoie S, Grunstein M . Genome-wide binding map of the histone deacetylase Rpd3 in yeast. Nat Genet. 2002; 31(3):248-54. DOI: 10.1038/ng907. View

14.

Alland L, David G, Shen-Li H, Potes J, Muhle R, Lee H . Identification of mammalian Sds3 as an integral component of the Sin3/histone deacetylase corepressor complex. Mol Cell Biol. 2002; 22(8):2743-50. PMC: 133736. DOI: 10.1128/MCB.22.8.2743-2750.2002. View

15.

Jamieson K, McNaught K, Ormsby T, Leggett N, Honda S, Selker E . Telomere repeats induce domains of H3K27 methylation in Neurospora. Elife. 2018; 7. PMC: 5752202. DOI: 10.7554/eLife.31216. View

16.

Zylicz J, Bousard A, Zumer K, Dossin F, Mohammad E, da Rocha S . The Implication of Early Chromatin Changes in X Chromosome Inactivation. Cell. 2019; 176(1-2):182-197.e23. PMC: 6333919. DOI: 10.1016/j.cell.2018.11.041. View

17.

Shaver S, Casas-Mollano J, Cerny R, Cerutti H . Origin of the polycomb repressive complex 2 and gene silencing by an E(z) homolog in the unicellular alga Chlamydomonas. Epigenetics. 2010; 5(4):301-12. DOI: 10.4161/epi.5.4.11608. View

18.

Tie F, Banerjee R, Stratton C, Prasad-Sinha J, Stepanik V, Zlobin A . CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing. Development. 2009; 136(18):3131-41. PMC: 2730368. DOI: 10.1242/dev.037127. View

19.

van der Vlag J, Otte A . Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation. Nat Genet. 1999; 23(4):474-8. DOI: 10.1038/70602. View

20.

Lechner T, Carrozza M, Yu Y, Grant P, Eberharter A, Vannier D . Sds3 (suppressor of defective silencing 3) is an integral component of the yeast Sin3[middle dot]Rpd3 histone deacetylase complex and is required for histone deacetylase activity. J Biol Chem. 2000; 275(52):40961-6. DOI: 10.1074/jbc.M005730200. View