Histone Sumoylation Promotes Set3 Histone-deacetylase Complex-mediated Transcriptional Regulation

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2020 Nov 24

PMID 33231641

Citations 30

Authors

Hong-Yeoul Ryu

Dejian Zhao

Jianhui Li

Dan Su

Mark Hochstrasser

Affiliations

Soon will be listed here.

Abstract

Histones are substrates of the SUMO (small ubiquitin-like modifier) conjugation pathway. Several reports suggest histone sumoylation affects transcription negatively, but paradoxically, our genome-wide analysis shows the modification concentrated at many active genes. We find that trans-tail regulation of histone-H2B ubiquitylation and H3K4 di-methylation potentiates subsequent histone sumoylation. Consistent with the known control of the Set3 histone deacetylase complex (HDAC) by H3K4 di-methylation, histone sumoylation directly recruits the Set3 complex to both protein-coding and noncoding RNA (ncRNA) genes via a SUMO-interacting motif in the HDAC Cpr1 subunit. The altered gene expression profile caused by reducing histone sumoylation matches well to the profile in cells lacking Set3. Histone H2B sumoylation and the Set3 HDAC coordinately suppress cryptic ncRNA transcription initiation internal to mRNA genes. Our results reveal an elaborate co-transcriptional histone crosstalk pathway involving the consecutive ubiquitylation, methylation, sumoylation and deacetylation of histones, which maintains transcriptional fidelity by suppressing spurious transcription.

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References

Ryu H, Su D, Wilson-Eisele N, Zhao D, Lopez-Giraldez F, Hochstrasser M . The Ulp2 SUMO protease promotes transcription elongation through regulation of histone sumoylation. EMBO J. 2019; 38(16):e102003. PMC: 6694223. DOI: 10.15252/embj.2019102003. View

Love M, Huber W, Anders S . Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15(12):550. PMC: 4302049. DOI: 10.1186/s13059-014-0550-8. View

Neil H, Malabat C, dAubenton-Carafa Y, Xu Z, Steinmetz L, Jacquier A . Widespread bidirectional promoters are the major source of cryptic transcripts in yeast. Nature. 2009; 457(7232):1038-42. DOI: 10.1038/nature07747. View

Ryu H, Ahn S . Yeast histone H3 lysine 4 demethylase Jhd2 regulates mitotic rDNA condensation. BMC Biol. 2014; 12:75. PMC: 4201760. DOI: 10.1186/s12915-014-0075-3. View

Tisseur M, Kwapisz M, Morillon A . Pervasive transcription - Lessons from yeast. Biochimie. 2011; 93(11):1889-96. DOI: 10.1016/j.biochi.2011.07.001. View

Matafora V, DAmato A, Mori S, Blasi F, Bachi A . Proteomics analysis of nucleolar SUMO-1 target proteins upon proteasome inhibition. Mol Cell Proteomics. 2009; 8(10):2243-55. PMC: 2758753. DOI: 10.1074/mcp.M900079-MCP200. View

Hannich J, Lewis A, Kroetz M, Li S, Heide H, Emili A . Defining the SUMO-modified proteome by multiple approaches in Saccharomyces cerevisiae. J Biol Chem. 2004; 280(6):4102-10. DOI: 10.1074/jbc.M413209200. View

van Dijk E, Chen C, dAubenton-Carafa Y, Gourvennec S, Kwapisz M, Roche V . XUTs are a class of Xrn1-sensitive antisense regulatory non-coding RNA in yeast. Nature. 2011; 475(7354):114-7. DOI: 10.1038/nature10118. View

Schneider J, Wood A, Lee J, Schuster R, Dueker J, Maguire C . Molecular regulation of histone H3 trimethylation by COMPASS and the regulation of gene expression. Mol Cell. 2005; 19(6):849-56. DOI: 10.1016/j.molcel.2005.07.024. View

10.

Ryu H, Wilson N, Mehta S, Hwang S, Hochstrasser M . Loss of the SUMO protease Ulp2 triggers a specific multichromosome aneuploidy. Genes Dev. 2016; 30(16):1881-94. PMC: 5024685. DOI: 10.1101/gad.282194.116. View

11.

Buratowski S, Kim T . The role of cotranscriptional histone methylations. Cold Spring Harb Symp Quant Biol. 2011; 75:95-102. PMC: 3229092. DOI: 10.1101/sqb.2010.75.036. View

12.

Kim T, Buratowski S . Two Saccharomyces cerevisiae JmjC domain proteins demethylate histone H3 Lys36 in transcribed regions to promote elongation. J Biol Chem. 2007; 282(29):20827-35. DOI: 10.1074/jbc.M703034200. View

13.

Chymkowitch P, Nguea A, Aanes H, Koehler C, Thiede B, Lorenz S . Sumoylation of Rap1 mediates the recruitment of TFIID to promote transcription of ribosomal protein genes. Genome Res. 2015; 25(6):897-906. PMC: 4448685. DOI: 10.1101/gr.185793.114. View

14.

Dhall A, Weller C, Chu A, Shelton P, Chatterjee C . Chemically Sumoylated Histone H4 Stimulates Intranucleosomal Demethylation by the LSD1-CoREST Complex. ACS Chem Biol. 2017; 12(9):2275-2280. PMC: 5726507. DOI: 10.1021/acschembio.7b00716. View

15.

Zhao J . Sumoylation regulates diverse biological processes. Cell Mol Life Sci. 2007; 64(23):3017-33. PMC: 7079795. DOI: 10.1007/s00018-007-7137-4. View

16.

Sun Z, Allis C . Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast. Nature. 2002; 418(6893):104-8. DOI: 10.1038/nature00883. View

17.

Nathan D, Ingvarsdottir K, Sterner D, Bylebyl G, Dokmanovic M, Dorsey J . Histone sumoylation is a negative regulator in Saccharomyces cerevisiae and shows dynamic interplay with positive-acting histone modifications. Genes Dev. 2006; 20(8):966-76. PMC: 1472304. DOI: 10.1101/gad.1404206. View

18.

Wery M, Descrimes M, Vogt N, Dallongeville A, Gautheret D, Morillon A . Nonsense-Mediated Decay Restricts LncRNA Levels in Yeast Unless Blocked by Double-Stranded RNA Structure. Mol Cell. 2016; 61(3):379-392. PMC: 4747904. DOI: 10.1016/j.molcel.2015.12.020. View

19.

Jensen T, Jacquier A, Libri D . Dealing with pervasive transcription. Mol Cell. 2013; 52(4):473-84. DOI: 10.1016/j.molcel.2013.10.032. View

20.

Gilbert T, McDaniel S, Byrum S, Cades J, Dancy B, Wade H . A PWWP domain-containing protein targets the NuA3 acetyltransferase complex via histone H3 lysine 36 trimethylation to coordinate transcriptional elongation at coding regions. Mol Cell Proteomics. 2014; 13(11):2883-95. PMC: 4223479. DOI: 10.1074/mcp.M114.038224. View