Unravelling the role of Set2 protein domains in H3K36 methylation in Saccharomyces cerevisiae

Authors

  • Saima Nazir Department of Biochemistry; University of Kashmir
  • Urseela Yasien Centre for Interdisciplinary Research and Innovations (CIRI); University of Kashmir
  • Aaqib Ashraf Department of Clinical Biochemistry; University of Kashmir
  • Showkat Ahmad Ganie Department of Clinical Biochemistry; University of Kashmir
  • Abdul Wajid Bhat Centre for Interdisciplinary Research and Innovations (CIRI); Department of Clinical Biochemistry, University of Kashmir,

DOI:

https://doi.org/10.22364/eeb.22.09

Keywords:

halophyte, ion accumulation, Mertensia maritima, mineral nutrition, propagation, salinity, temporary immersion system, tissue culture

Abstract

Histone methylation plays a crucial role in gene expression and chromatin structure regulation. In Saccharomyces cerevisiae, the Set2 protein is responsible for the methylation of histone H3 at lysine 36 (H3K36), which is associated with transcriptional regulation, RNA processing, and DNA repair. This study investigates the specific functions of individual domains within the yeast Set2 protein by utilizing PCR-based domain deletions and subsequent western blot analysis to assess their impact on H3K36 methylation status. The results demonstrate that the SET domain alone is sufficient for H3K36 dimethylation, while optimal trimethylation necessitates the presence of additional domains, including the central autoinhibitory domain. Furthermore, the SRI domain is found to be essential for both di- and trimethylation when considering the full-length Set2 protein. These findings underscore the critical role of Set2 domains in modulating Set2 enzymatic activity.

References

Avvakumov N., Nourani A., Cote J. 2011. Histone chaperones: modulators of chromatin marks. Mol. Cell 41: 502–514.

Bannister A.J., Kouzarides T. 2011. Regulation of chromatin by histone modifications. Cell Res. 21: 381–395.

Carey M., Li B., Workman J.L. 2006. RSC exploits histone acetylation to abrogate the nucleosomal block to RNA polymerase II elongation. Mol. Cell 24: 481–487.

Carrozza M.J., Li B., Florens L., Suganuma T., Swanson S.K., Lee K.K., Shia W.J., Anderson S., Yates J., Washburn M.P., Workman J.L. 2005. Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell 123: 581–592.

Clapier C.R., Cairns B.R. 2009. The biology of chromatin remodeling complexes. Annu. Rev. Biochem. 78: 273–304.

Dahiya R., Mohammad T., Alajmi M.F., Rehman M.T., Hasan G.M., Hussain A., Hassan M.I. 2020. Insights into the conserved regulatory mechanisms of human and yeast aging. Biomolecules 10: 882.

Davey C.A., Sargent D.F., Luger K., Maeder A.W., Richmond T.J. 2002. Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 Å resolution. J. Mol. Biol. 319: 1097–1113.

Du H.N., Fingerman I.M., Briggs S.D. 2008. Histone H3 K36 methylation is mediated by a trans-histone methylation pathway involving an interaction between Set2 and histone H4. Genes Dev. 22: 2786–2798.

Duns G., van den Berg E., van Duivenbode I., Osinga J., Hollema H., Hofstra R.M., Kok K. 2010. Histone methyltransferase gene SETD2 is a novel tumor suppressor gene in clear cell renal cell carcinoma. Cancer Res. 70: 4287–4291.

Edmunds J.W., Mahadevan L.C., Clayton A.L. 2008. Dynamic histone H3 methylation during gene induction: HYPB/Setd2 mediates all H3K36 trimethylation. EMBO J. 27: 406–420.

Fahey C.C., Davis I.J. 2017. SETting the stage for cancer development: SETD2 and the consequences of lost methylation. Cold Spring Harb. Perspect. Med. 7: a026468.

Flaus A., Owen-Hughes T. 2004. Mechanisms for ATP-dependent chromatin remodelling: farewell to the tuna-can octamer? Curr. Opin. Genet. Dev. 14: 165–173.

Frigerio C., Di Nisio E., Galli M., Colombo C.V., Negri R., Clerici M. 2023. The chromatin landscape around DNA double-strand breaks in yeast and its influence on DNA repair pathway choice. Int. J. Mol. Sci. 24

Gurard-Levin Z.A., Quivy J.P., Almouzni G. 2014. Histone chaperones: assisting histone traffic and nucleosome dynamics. Annu. Rev. Biochem. 83: 487–517.

Hammond C.M., Stromme C.B., Huang H., Patel D.J., Groth A. 2017. Histone chaperone networks shaping chromatin function. Nature Rev. Mol. Cell. Biol. 18: 141–158.

Jha D.K., Strahl B.D. 2014. An RNA polymerase II-coupled function for histone H3K36 methylation in checkpoint activation and DSB repair. Nature Commun. 5: 3965.

Kim J.H., Lee B.B., Oh Y.M., Zhu C., Steinmetz L.M., Lee Y., Kim W.K., Lee S.B., Buratowski S., Kim T. 2016. Modulation of mRNA and lncRNA expression dynamics by the Set2-Rpd3S pathway. Nature Commun. 7: 13534.

Kingston R.E., Bunker C.A., Imbalzano A.N. 1996. Repression and activation by multiprotein complexes that alter chromatin structure. Genes Dev. 10: 905–920.

Kizer K.O., Phatnani H.P., Shibata Y., Hall H., Greenleaf A.L., Strahl B.D. 2005. A novel domain in Set2 mediates RNA polymerase II interaction and couples histone H3 K36 methylation with transcript elongation. Mol. Cell. Biol. 25: 3305–3316.

Kouzarides T. 2007. Chromatin modifications and their function. Cell 128: 693–705.

Krogan N.J., Kim M., Tong A., Golshani A., Cagney G., Canadien V., Richards D.P., Beattie B.K., Emili A., Boone C., Shilatifard A., Buratowski S., Greenblatt J. 2003. Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II. Mol. Cell. Biol. 23: 4207–4218.

Kulaeva O.I., Gaykalova D.A., Pestov N.A., Golovastov V.V., Vassylyev D.G., Artsimovitch I., Studitsky V.M. 2009. Mechanism of chromatin remodeling and recovery during passage of RNA polymerase II. Nature Struct. Mol. Biol. 16: 1272–1278.

Kulaeva O.I., Hsieh F.K., Studitsky V.M. 2010. RNA polymerase complexes cooperate to relieve the nucleosomal barrier and evict histones. Proc. Natl. Acad. Sci. USA 107: 11325–11330.

Lam U.T.F., Chen E.S. 2022. Molecular mechanisms in governing genomic stability and tumor suppression by the SETD2 H3K36 methyltransferase. Int. J. Biochem. Cell. Biol. 144: 106155.

Lam U.T.F., Tan B.K.Y., Poh J.J.X., Chen E.S. 2022. Structural and functional specificity of H3K36 methylation. Epigenet. Chromat. 15: 17.

Lee J.S., Shilatifard A. 2007. A site to remember: H3K36 methylation a mark for histone deacetylation. Mutat. Res. 618: 130–134.

Li B., Howe L., Anderson S., Yates J.R., 3rd, Workman J.L. 2003. The Set2 histone methyltransferase functions through the phosphorylated carboxyl-terminal domain of RNA polymerase II. J. Biol. Chem. 278: 8897–8903.

Li J., Kluiver J., Osinga J., Westers H., van Werkhoven M.B., Seelen M.A., Sijmons R.H., van den Berg A., Kok K. 2016. Functional studies on primary tubular epithelial cells indicate a tumor suppressor role of SETD2 in clear cell renal cell carcinoma. Neoplasia 18: 339–346.

Lim K.K., Nguyen T.T.T., Li A.Y., Yeo Y.P., Chen E.S. 2018. Histone H3 lysine 36 methyltransferase mobilizes NER factors to regulate tolerance against alkylation damage in fission yeast. Nucleic Acids Res. 46: 5061–5074.

Luger K., Mader A.W., Richmond R.K., Sargent D.F., Richmond T.J. 1997. Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 389: 251–260.

Ma C., Liu M., Feng W., Rao H., Zhang W., Liu C., Xu Y., Wang Z., Teng Y., Yang X., Ni L., Xu J., Gao W.Q., Lu B., Li L. 2023. Loss of SETD2 aggravates colorectal cancer progression caused by SMAD4 deletion through the RAS/ERK signalling pathway. Clin. Transl. Med. 13: e1475.

Marino-Ramirez L., Jordan I.K., Landsman D. 2006. Multiple independent evolutionary solutions to core histone gene regulation. Genome Biol. 7: R122.

McDaniel S.L., Hepperla A.J., Huang J., Dronamraju R., Adams A.T., Kulkarni V.G., Davis I.J., Strahl B.D. 2017. H3K36 methylation regulates nutrient stress response in Saccharomyces cerevisiae by enforcing transcriptional fidelity. Cell Rep. 19: 2371–2382.

Niu N., Lu P., Yang Y., He R., Zhang L., Shi J., Wu J., Yang M., Zhang Z.G., Wang L.W., Gao W.Q., Habtezion A., Xiao G.G., Sun Y., Li L., Xue J. 2020. Loss of Setd2 promotes Kras-induced acinar-to-ductal metaplasia and epithelia-mesenchymal transition during pancreatic carcinogenesis. Gut 69: 715–726.

Pai C.C., Deegan R.S., Subramanian L., Gal C., Sarkar S., Blaikley E.J., Walker C., Hulme L., Bernhard E., Codlin S., Bahler J., Allshire R., Whitehall S., Humphrey T.C. 2014. A histone H3K36 chromatin switch coordinates DNA double-strand break repair pathway choice. Nature Commun. 5: 4091.

Pai C.C., Kishkevich A., Deegan R.S., Keszthelyi A., Folkes L., Kearsey S.E., De Leon N., Soriano I., de Bruin R.A.M., Carr A.M., Humphrey T.C. 2017. Set2 methyltransferase facilitates DNA replication and promotes genotoxic stress responses through MBF-dependent transcription. Cell Rep. 20: 2693–2705.

Paranjape S.M., Kamakaka R.T., Kadonaga J.T. 1994. Role of chromatin structure in the regulation of transcription by RNA polymerase II. Annu. Rev. Biochem. 63: 265–297.

Pfister S.X., Ahrabi S., Zalmas L.P., Sarkar S., Aymard F., Bachrati C.Z., Helleday T., Legube G., La Thangue N.B., Porter A.C., Humphrey T.C. 2014. SETD2-dependent histone H3K36 trimethylation is required for homologous recombination repair and genome stability. Cell Rep. 7: 2006–2018.

Pryde F., Jain D., Kerr A., Curley R., Mariotti F.R., Vogelauer M. 2009. H3 k36 methylation helps determine the timing of cdc45 association with replication origins. PLoS One 4: e5882.

Putnam C.D., Allen-Soltero S.R., Martinez S.L., Chan J.E., Hayes T.K., Kolodner R.D. 2012. Bioinformatic identification of genes suppressing genome instability. Proc. Natl. Acad. Sci. USA 109: E3251–3259.

Ruthenburg A.J., Li H., Patel D.J., Allis C.D. 2007. Multivalent engagement of chromatin modifications by linked binding modules. Nature Rev. Mol. Cell. Biol. 8: 983–994.

Saha A., Wittmeyer J., Cairns B.R. 2006. Chromatin remodelling: the industrial revolution of DNA around histones. Nature Rev. Mol. Cell. Biol. 7: 437–447.

Sharda A., Humphrey T.C. 2022. The role of histone H3K36me3 writers, readers and erasers in maintaining genome stability. DNA Repair 119: 103407.

Smith C.L., Peterson C.L. 2005. ATP-dependent chromatin remodeling. In: Schatten G.P. (Ed.) Current Topics in Developmental Biology. Vol. 65. Elsevier Academic Press, Amsterdam, pp. 115–148.

Strahl B.D., Grant P.A., Briggs S.D., Sun Z.W., Bone J.R., Caldwell J.A., Mollah S., Cook R.G., Shabanowitz J., Hunt D.F., Allis C.D. 2002. Set2 is a nucleosomal histone H3-selective methyltransferase that mediates transcriptional repression. Mol. Cell. Biol. 22: 1298–1306.

Tsang J.Y., Lai S.T., Ni Y.B., Shao Y., Poon I.K., Kwan J.S., Chow C., Shea K.H., Tse G.M. 2021. SETD2 alterations and histone H3K36 trimethylation in phyllodes tumor of breast. Breast Cancer Res. Treat. 187: 339–347.

Tsukiyama T., Wu C. 1997. Chromatin remodeling and transcription. Curr. Opin. Genet. Dev. 7: 182–191.

van Steensel B. 2011. Chromatin: constructing the big picture. EMBO J. 30: 1885–1895.

Venkatesh S., Workman J.L. 2013. Set2 mediated H3 lysine 36 methylation: regulation of transcription elongation and implications in organismal development. WIRES Dev. Biol. 2: 685–700.

Wagner E.J., Carpenter P.B. 2012. Understanding the language of Lys36 methylation at histone H3. Nature Rev. Mol. Cell. Biol. 13: 115–126.

Wen H., Li Y., Xi Y., Jiang S., Stratton S., Peng D., Tanaka K., Ren Y., Xia Z., Wu J., Li B., Barton M.C., Li W., Li H., Shi X. 2014. ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression. Nature 508: 263–268.

Winston F., Dollard C., Ricupero-Hovasse S.L. 1995. Construction of a set of convenient Saccharomyces cerevisiae strains that are isogenic to S288C. Yeast 11: 53–55.

Workman J.L. 2006. Nucleosome displacement in transcription. Genes Dev. 20: 2009–2017.

Xiao C., Fan T., Tian H., Zheng Y., Zhou Z., Li S., Li C., He J. 2021. H3K36 trimethylation-mediated biological functions in cancer. Clin. Epigenet. 13: 199.

Xiao T,. Hall H., Kizer K.O., Shibata Y., Hall M.C., Borchers C.H., Strahl B.D. 2003. Phosphorylation of RNA polymerase II CTD regulates H3 methylation in yeast. Genes Dev. 17: 654–663.

Yang X., Chen R., Chen Y., Zhou Y., Wu C., Li Q., Wu J., Hu W.W., Zhao W.Q., Wei W., Shi J.T., Ji M. 2022. Methyltransferase SETD2 inhibits tumor growth and metastasis via STAT1-IL-8 signaling-mediated epithelial-mesenchymal transition in lung adenocarcinoma. Cancer Sci. 113: 1195–1207.

Youdell M.L., Kizer K.O., Kisseleva-Romanova E., Fuchs S.M., Duro E., Strahl B.D., Mellor J. 2008. Roles for Ctk1 and Spt6 in regulating the different methylation states of histone H3 lysine 36. Mol. Cell. Biol. 28: 4915–4926.

Yuan W., Xie J., Long C., Erdjument-Bromage H., Ding X., Zheng Y., Tempst P., Chen S., Zhu B., Reinberg D. 2009. Heterogeneous nuclear ribonucleoprotein L is a subunit of human KMT3a/Set2 complex required for H3 Lys-36 trimethylation activity in vivo. J. Biol. Chem. 284: 15701–15707.

Zhou Y., Zheng X., Xu B., Deng H., Chen L., Jiang J. 2020. Histone methyltransferase SETD2 inhibits tumor growth via suppressing CXCL1-mediated activation of cell cycle in lung adenocarcinoma. Aging 12: 25189–25206.

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Published

2024-06-20

How to Cite

Nazir, S., Yasien, U., Ashraf, A., Ganie, S. A., & Bhat, A. W. (2024). Unravelling the role of Set2 protein domains in H3K36 methylation in Saccharomyces cerevisiae. Environmental and Experimental Biology, 22(2), 87–93. https://doi.org/10.22364/eeb.22.09

Issue

Vol. 22 No. 2 (2024): Environmental and Experimental Biology

Section

Original Papers

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