Advertisement

SET domains and stress: uncovering new functions for yeast Set4

  • Khoa Tran
  • Erin M. Green
Mini-Review

Abstract

Chromatin dynamics are central to the regulation of gene expression and genome stability, particularly in the presence of environmental signals or stresses that prompt rapid reprogramming of the genome to promote survival or differentiation. While numerous chromatin regulators have been implicated in modulating cellular responses to stress, gaps in our mechanistic understanding of chromatin-based changes during stress suggest that additional proteins are likely critical to these responses and the molecular details underlying their activities are unclear in many cases. We recently identified a role for the relatively uncharacterized SET domain protein Set4 in promoting cell survival during oxidative stress in Saccharomyces cerevisiae. Set4 is a member of the Set3 subfamily of SET domain proteins which are defined by the presence of a PHD finger and divergent SET domain sequences. Here, we integrate our new observations on the function of Set4 with known roles for other related family members, including yeast Set3, fly UpSET and mammalian proteins MLL5 and SETD5. We discuss outstanding questions regarding the molecular mechanisms by which these proteins control gene expression and their potential contributions to cellular responses to environmental stress.

Keywords

Chromatin SET domain PHD finger Stress responses Oxidative stress Gene expression Set4 Budding yeast 

Notes

Acknowledgements

The authors acknowledge support from the National Institutes of Health Grant R01GM124342 to E.M.G.

References

  1. Ali M, Rincón-Arano H, Zhao W, Rothbart SB, Tong Q, Parkhurst SM, Strahl BD, Deng LW, Groudine M, Kutateladze TG (2013) Molecular basis for chromatin binding and regulation of MLL5. Proc Natl Acad Sci USA 110:11296–11301.  https://doi.org/10.1073/pnas.1310156110 CrossRefPubMedGoogle Scholar
  2. Aragon AD, Rodriguez AL, Meirelles O, Roy S, Davidson GS, Tapia PH, Allen C, Joe R, Benn D, Werner-Washburne M (2008) Characterization of differentiated quiescent and nonquiescent cells in yeast stationary-phase cultures. Mol Biol Cell 19:1271–1280.  https://doi.org/10.1091/mbc.E07-07-0666 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Calpena E, Palau F, Espinós C, Galindo MI (2015) Evolutionary history of the Smyd gene family in metazoans: a framework to identify the orthologs of human Smyd genes in Drosophila and other animal species. PLoS One 10:e0134106.  https://doi.org/10.1371/journal.pone.0134106 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Cheng F, Liu J, Zhou SH, Wang XN, Chew JF, Deng LW (2008) RNA interference against mixed lineage leukemia 5 resulted in cell cycle arrest. Int J Biochem Cell Biol 40:2472–2481.  https://doi.org/10.1016/j.biocel.2008.04.012 CrossRefPubMedGoogle Scholar
  5. Chi P, Allis CD, Wang GG (2010) Covalent histone modifications–miswritten, misinterpreted and mis-erased in human cancers. Nat Rev Cancer 10:457–469.  https://doi.org/10.1038/nrc2876 CrossRefPubMedPubMedCentralGoogle Scholar
  6. Clarke SG (2013) Protein methylation at the surface and buried deep: thinking outside the histone box. Trends Biochem Sci 38:243–252.  https://doi.org/10.1016/j.tibs.2013.02.004 CrossRefPubMedPubMedCentralGoogle Scholar
  7. D’Urso A, Brickner JH (2017) Epigenetic transcriptional memory. Curr Genet 63:435–439.  https://doi.org/10.1007/s00294-016-0661-8 CrossRefPubMedGoogle Scholar
  8. Deliu E, Arecco N, Morandell J, Dotter CP, Contreras X, Girardot C, Käsper EL, Kozlova A, Kishi K, Chiaradia I, Noh KM, Novarino G (2018) Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nat Neurosci.  https://doi.org/10.1038/s41593-018-0266-2 CrossRefPubMedGoogle Scholar
  9. Deng LW, Chiu I, Strominger JL (2004) MLL 5 protein forms intranuclear foci, and overexpression inhibits cell cycle progression. Proc Natl Acad Sci USA 101:757–762.  https://doi.org/10.1073/pnas.2036345100 CrossRefPubMedGoogle Scholar
  10. Dillon SC, Zhang X, Trievel RC, Cheng X (2005) The SET-domain protein superfamily: protein lysine methyltransferases. Genome Biol 6:227.  https://doi.org/10.1186/gb-2005-6-8-227 CrossRefPubMedPubMedCentralGoogle Scholar
  11. Ding X, Jiang W, Zhou P, Liu L, Wan X, Yuan X, Wang X, Chen M, Chen J, Yang J, Kong C, Li B, Peng C, Wong CC, Hou F, Zhang Y (2015) Mixed lineage leukemia 5 (MLL5) protein stability is cooperatively regulated by O-GlcNac transferase (OGT) and ubiquitin specific protease 7 (USP7). PLoS One 10:e0145023.  https://doi.org/10.1371/journal.pone.0145023 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Gatchalian J, Ali M, Andrews FH, Zhang Y, Barrett AS, Kutateladze TG (2017) Structural insight into recognition of methylated histone H3K4 by Set3. J Mol Biol 429:2066–2074.  https://doi.org/10.1016/j.jmb.2016.09.020 CrossRefPubMedGoogle Scholar
  13. Ghaemmaghami S, Huh WK, Bower K, Howson RW, Belle A, Dephoure N, O’Shea EK, Weissman JS (2003) Global analysis of protein expression in yeast. Nature 425:737–741.  https://doi.org/10.1038/nature02046 CrossRefPubMedGoogle Scholar
  14. Green EM, Mas G, Young NL, Garcia BA, Gozani O (2012) Methylation of H4 lysines 5, 8 and 12 by yeast Set5 calibrates chromatin stress responses. Nat Struct Mol Biol 19:361–363.  https://doi.org/10.1038/nsmb.2252 CrossRefPubMedPubMedCentralGoogle Scholar
  15. Grozeva D, Carss K, Spasic-Boskovic O, Parker MJ, Archer H, Firth HV, Park SM, Canham N, Holder SE, Wilson M, Hackett A, Field M, Floyd JA, Hurles M, Raymond FL, Consortium UK (2014) De novo loss-of-function mutations in SETD5, encoding a methyltransferase in a 3p25 microdeletion syndrome critical region, cause intellectual disability. Am J Hum Genet 94:618–624.  https://doi.org/10.1016/j.ajhg.2014.03.006 CrossRefPubMedPubMedCentralGoogle Scholar
  16. Heuser M, Yap DB, Leung M, de Algara TR, Tafech A, McKinney S, Dixon J, Thresher R, Colledge B, Carlton M, Humphries RK, Aparicio SA (2009) Loss of MLL5 results in pleiotropic hematopoietic defects, reduced neutrophil immune function, and extreme sensitivity to DNA demethylation. Blood 113:1432–1443.  https://doi.org/10.1182/blood-2008-06-162263 CrossRefPubMedGoogle Scholar
  17. Jaiswal D, Turniansky R, Green EM (2017) Choose your own adventure: the role of histone modifications in yeast cell fate. J Mol Biol 429:1946–1957.  https://doi.org/10.1016/j.jmb.2016.10.018 CrossRefPubMedGoogle Scholar
  18. Jezek M, Gast A, Choi G, Kulkarni R, Quijote J, Graham-Yooll A, Park D, Green EM (2017) The histone methyltransferases Set5 and Set1 have overlapping functions in gene silencing and telomere maintenance. Epigenetics 12:93–104.  https://doi.org/10.1080/15592294.2016.1265712 CrossRefPubMedGoogle Scholar
  19. Kemmeren P, Sameith K, van de Pasch LA, Benschop JJ, Lenstra TL, Margaritis T, O’Duibhir E, Apweiler E, van Wageningen S, Ko CW, van Heesch S, Kashani MM, Ampatziadis-Michailidis G, Brok MO, Brabers NA, Miles AJ, Bouwmeester D, van Hooff SR, van Bakel H, Sluiters E, Bakker LV, Snel B, Lijnzaad P, van Leenen D, Groot Koerkamp MJ, Holstege FC (2014) Large-scale genetic perturbations reveal regulatory networks and an abundance of gene-specific repressors. Cell 157:740–752.  https://doi.org/10.1016/j.cell.2014.02.054 CrossRefPubMedGoogle Scholar
  20. Kim T, Buratowski S (2009) Dimethylation of H3K4 by Set1 recruits the Set3 histone deacetylase complex to 5′ transcribed regions. Cell 137:259–272.  https://doi.org/10.1016/j.cell.2009.02.045 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Kim T, Xu Z, Clauder-Münster S, Steinmetz LM, Buratowski S (2012) Set3 HDAC mediates effects of overlapping noncoding transcription on gene induction kinetics. Cell 150:1158–1169.  https://doi.org/10.1016/j.cell.2012.08.016 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Kuechler A, Zink AM, Wieland T, Lüdecke HJ, Cremer K, Salviati L, Magini P, Najafi K, Zweier C, Czeschik JC, Aretz S, Endele S, Tamburrino F, Pinato C, Clementi M, Gundlach J, Maylahn C, Mazzanti L, Wohlleber E, Schwarzmayr T, Kariminejad R, Schlessinger A, Wieczorek D, Strom TM, Novarino G, Engels H (2015) Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome. Eur J Hum Genet 23:753–760.  https://doi.org/10.1038/ejhg.2014.165 CrossRefPubMedGoogle Scholar
  23. Lai LC, Kosorukoff AL, Burke PV, Kwast KE (2006) Metabolic-state-dependent remodeling of the transcriptome in response to anoxia and subsequent reoxygenation in Saccharomyces cerevisiae. Eukaryot Cell 5:1468–1489.  https://doi.org/10.1128/EC.00107-06 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Lemak A, Yee A, Wu H, Yap D, Zeng H, Dombrovski L, Houliston S, Aparicio S, Arrowsmith CH (2013) Solution NMR structure and histone binding of the PHD domain of human MLL5. PLoS One 8:e77020.  https://doi.org/10.1371/journal.pone.0077020 CrossRefPubMedPubMedCentralGoogle Scholar
  25. Liu J, Cheng F, Deng LW (2012) MLL5 maintains genomic integrity by regulating the stability of the chromosomal passenger complex through a functional interaction with Borealin. J Cell Sci 125:4676–4685.  https://doi.org/10.1242/jcs.110411 CrossRefPubMedPubMedCentralGoogle Scholar
  26. Madan V, Madan B, Brykczynska U, Zilbermann F, Hogeveen K, Döhner K, Döhner H, Weber O, Blum C, Rodewald HR, Sassone-Corsi P, Peters AH, Fehling HJ (2009) Impaired function of primitive hematopoietic cells in mice lacking the mixed-lineage-leukemia homolog MLL5. Blood 113:1444–1454.  https://doi.org/10.1182/blood-2008-02-142638 CrossRefPubMedGoogle Scholar
  27. Martín GM, King DA, Green EM, Garcia-Nieto PE, Alexander R, Collins SR, Krogan NJ, Gozani OP, Morrison AJ (2014) Set5 and Set1 cooperate to repress gene expression at telomeres and retrotransposons. Epigenetics 9:513–522.  https://doi.org/10.4161/epi.27645 CrossRefPubMedPubMedCentralGoogle Scholar
  28. Mas-Y-Mas S, Barbon M, Teyssier C, Déméné H, Carvalho JE, Bird LE, Lebedev A, Fattori J, Schubert M, Dumas C, Bourguet W, le Maire A (2016) The Human mixed lineage leukemia 5 (MLL5), a sequentially and structurally divergent SET domain-containing protein with no intrinsic catalytic activity. PLoS One 11:e0165139.  https://doi.org/10.1371/journal.pone.0165139 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Matsuo R, Mizobuchi S, Nakashima M, Miki K, Ayusawa D, Fujii M (2017) Central roles of iron in the regulation of oxidative stress in the yeast Saccharomyces cerevisiae. Curr Genet 63:895–907.  https://doi.org/10.1007/s00294-017-0689-4 CrossRefPubMedGoogle Scholar
  30. Maze I, Noh KM, Soshnev AA, Allis CD (2014) Every amino acid matters: essential contributions of histone variants to mammalian development and disease. Nat Rev Genet 15:259–271.  https://doi.org/10.1038/nrg3673 CrossRefPubMedPubMedCentralGoogle Scholar
  31. McDaniel SL, Hepperla AJ, Huang J, Dronamraju R, Adams AT, Kulkarni VG, Davis IJ, Strahl BD (2017) H3K36 methylation regulates nutrient stress response in Saccharomyces cerevisiae by enforcing transcriptional fidelity. Cell Rep 19:2371–2382.  https://doi.org/10.1016/j.celrep.2017.05.057 CrossRefPubMedPubMedCentralGoogle Scholar
  32. McElroy KA, Jung YL, Zee BM, Wang CI, Park PJ, Kuroda MI (2017) upSET, the Drosophila homologue of SET3, is required for viability and the proper balance of active and repressive chromatin marks. G3 (Bethesda) 7: 625–635  https://doi.org/10.1534/g3.116.037788
  33. Nadal-Ribelles M, Mas G, Millán-Zambrano G, Solé C, Ammerer G, Chávez S, Posas F, de Nadal E (2015) H3K4 monomethylation dictates nucleosome dynamics and chromatin remodeling at stress-responsive genes. Nucleic Acids Res 43:4937–4949.  https://doi.org/10.1093/nar/gkv220 CrossRefPubMedPubMedCentralGoogle Scholar
  34. Osipovich AB, Gangula R, Vianna PG, Magnuson MA (2016) Setd5 is essential for mammalian development and the co-transcriptional regulation of histone acetylation. Development 143:4595–4607.  https://doi.org/10.1242/dev.141465 CrossRefPubMedPubMedCentralGoogle Scholar
  35. Pijnappel WW, Schaft D, Roguev A, Shevchenko A, Tekotte H, Wilm M, Rigaut G, Séraphin B, Aasland R, Stewart AF (2001) The S. cerevisiae SET3 complex includes two histone deacetylases, Hos2 and Hst1, and is a meiotic-specific repressor of the sporulation gene program. Genes Dev 15:2991–3004.  https://doi.org/10.1101/gad.207401 CrossRefPubMedPubMedCentralGoogle Scholar
  36. Porras-Yakushi TR, Whitelegge JP, Clarke S (2006) A novel SET domain methyltransferase in yeast: Rkm2-dependent trimethylation of ribosomal protein L12ab at lysine 10. J Biol Chem 281:35835–35845.  https://doi.org/10.1074/jbc.M606578200 CrossRefPubMedGoogle Scholar
  37. Rincon-Arano H, Halow J, Delrow JJ, Parkhurst SM, Groudine M (2012) UpSET recruits HDAC complexes and restricts chromatin accessibility and acetylation at promoter regions. Cell 151:1214–1228.  https://doi.org/10.1016/j.cell.2012.11.009 CrossRefPubMedPubMedCentralGoogle Scholar
  38. Searle NE, Pillus L (2018) Critical genomic regulation mediated by enhancer of polycomb. Curr Genet 64:147–154.  https://doi.org/10.1007/s00294-017-0742-3 CrossRefPubMedGoogle Scholar
  39. Searle NE, Torres-Machorro AL, Pillus L (2017) Chromatin regulation by the NuA4 acetyltransferase complex is mediated by essential interactions between enhancer of polycomb (Epl1) and Esa1. Genetics 205:1125–1137.  https://doi.org/10.1534/genetics.116.197830 CrossRefPubMedPubMedCentralGoogle Scholar
  40. Sebastian S, Sreenivas P, Sambasivan R, Cheedipudi S, Kandalla P, Pavlath GK, Dhawan J (2009) MLL5, a trithorax homolog, indirectly regulates H3K4 methylation, represses cyclin A2 expression, and promotes myogenic differentiation. Proc Natl Acad Sci USA 106:4719–4724.  https://doi.org/10.1073/pnas.0807136106 CrossRefPubMedGoogle Scholar
  41. Serratore ND, Baker KM, Macadlo LA, Gress AR, Powers BL, Atallah N, Westerhouse KM, Hall MC, Weake VM, Briggs SD (2018) A novel sterol-signaling pathway governs azole antifungal drug resistance and hypoxic gene repression in Saccharomyces cerevisiae. Genetics 208:1037–1055.  https://doi.org/10.1534/genetics.117.300554 CrossRefPubMedGoogle Scholar
  42. Shi X, Kachirskaia I, Walter KL, Kuo JH, Lake A, Davrazou F, Chan SM, Martin DG, Fingerman IM, Briggs SD, Howe L, Utz PJ, Kutateladze TG, Lugovskoy AA, Bedford MT, Gozani O (2007) Proteome-wide analysis in Saccharomyces cerevisiae identifies several PHD fingers as novel direct and selective binding modules of histone H3 methylated at either lysine 4 or lysine 36. J Biol Chem 282:2450–2455.  https://doi.org/10.1074/jbc.C600286200 CrossRefPubMedGoogle Scholar
  43. Soontorngun N (2017) Reprogramming of nonfermentative metabolism by stress-responsive transcription factors in the yeast Saccharomyces cerevisiae. Curr Genet 63:1–7.  https://doi.org/10.1007/s00294-016-0609-z CrossRefPubMedGoogle Scholar
  44. Tasdogan A, Kumar S, Allies G, Bausinger J, Beckel F, Hofemeister H, Mulaw M, Madan V, Scharfetter-Kochanek K, Feuring-Buske M, Doehner K, Speit G, Stewart AF, Fehling HJ (2016) DNA damage-Induced HSPC malfunction depends on ROS accumulation downstream of IFN-1 signaling and bid mobilization. Cell Stem Cell 19:752–767.  https://doi.org/10.1016/j.stem.2016.08.007 CrossRefPubMedGoogle Scholar
  45. Tee WW, Reinberg D (2014) Chromatin features and the epigenetic regulation of pluripotency states in ESCs. Development 141:2376–2390.  https://doi.org/10.1242/dev.096982 CrossRefPubMedPubMedCentralGoogle Scholar
  46. Tran K, Jethmalani Y, Jaiswal D, Green EM (2018) Set4 is a chromatin-associated protein, promotes survival during oxidative stress, and regulates stress response genes in yeast. J Biol Chem 293:14429–14443.  https://doi.org/10.1074/jbc.RA118.003078 CrossRefPubMedGoogle Scholar
  47. Weiner A, Chen HV, Liu CL, Rahat A, Klien A, Soares L, Gudipati M, Pfeffner J, Regev A, Buratowski S, Pleiss JA, Friedman N, Rando OJ (2012) Systematic dissection of roles for chromatin regulators in a yeast stress response. PLoS Biol 10:e1001369.  https://doi.org/10.1371/journal.pbio.1001369 CrossRefPubMedPubMedCentralGoogle Scholar
  48. Yap DB, Walker DC, Prentice LM, McKinney S, Turashvili G, Mooslehner-Allen K, de Algara TR, Fee J, de Tassigny X, Colledge WH, Aparicio S (2011) Mll5 is required for normal spermatogenesis. PLoS One 6:e27127.  https://doi.org/10.1371/journal.pone.0027127 CrossRefPubMedPubMedCentralGoogle Scholar
  49. Zhang Y, Wong J, Klinger M, Tran MT, Shannon KM, Killeen N (2009) MLL5 contributes to hematopoietic stem cell fitness and homeostasis. Blood 113:1455–1463.  https://doi.org/10.1182/blood-2008-05-159905 CrossRefPubMedPubMedCentralGoogle Scholar
  50. Zhou P, Wang Z, Yuan X, Zhou C, Liu L, Wan X, Zhang F, Ding X, Wang C, Xiong S, Yuan J, Li Q, Zhang Y (2013) Mixed lineage leukemia 5 (MLL5) protein regulates cell cycle progression and E2F1-responsive gene expression via association with host cell factor-1 (HCF-1). J Biol Chem 288:17532–17543.  https://doi.org/10.1074/jbc.M112.439729 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biological SciencesUniversity of Maryland Baltimore CountyBaltimoreUSA

Personalised recommendations