SUV39 SET domains mediate crosstalk of heterochromatic histone marks

Article Article scientifique Article SUV39 SET domains mediate crosstalk of heterochromatic histone marks eng 2021-09-15 author Stirpe Alessandro 0000-0002-2006-4066 Department of Molecular Biology, Faculty of Science, University of Geneva, Geneva, Switzerland. 837230 author Guidotti Nora Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. author Northall Sarah J Leicester Institute for Structural and Chemical Biology, University of Leicester, Leicester, United Kingdom.,Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom. author Kilic Sinan 0000-0001-5009-8884 Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. author Hainard Alexandre 0009-0006-7403-3261 University Medical Center, University of Geneva, Geneva, Switzerland. 635700 Services communs de la faculté de médecine (SCMU) author Vadas Oscar 0000-0003-3511-6479 School of Pharmaceutical Sciences, Faculty of Science, University of Geneva, Geneva, Switzerland. 508966 Département de microbiologie et médecine moléculaire (MIMOL) author Fierz Beat 0000-0002-2991-3044 Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. author Schalch Thomas 0000-0002-0758-3013 Department of Molecular Biology, Faculty of Science, University of Geneva, Geneva, Switzerland.,Leicester Institute for Structural and Chemical Biology, University of Leicester, Leicester, United Kingdom.,Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom. 787942 e62682 10.7554/eLife.62682 34524082 2050-084X PMC8443253 https://elifesciences.org/articles/62682 The SUV39 class of methyltransferase enzymes deposits histone H3 lysine 9 di- and trimethylation (H3K9me2/3), the hallmark of constitutive heterochromatin. How these enzymes are regulated to mark specific genomic regions as heterochromatic is poorly understood. Clr4 is the sole H3K9me2/3 methyltransferase in the fission yeast <i>Schizosaccharomyces pombe,</i> and recent evidence suggests that ubiquitination of lysine 14 on histone H3 (H3K14ub) plays a key role in H3K9 methylation. However, the molecular mechanism of this regulation and its role in heterochromatin formation remain to be determined. Our structure-function approach shows that the H3K14ub substrate binds specifically and tightly to the catalytic domain of Clr4, and thereby stimulates the enzyme by over 250-fold. Mutations that disrupt this mechanism lead to a loss of H3K9me2/3 and abolish heterochromatin silencing similar to <i>clr4</i> deletion. Comparison with mammalian SET domain proteins suggests that the Clr4 SET domain harbors a conserved sensor for H3K14ub, which mediates licensing of heterochromatin formation. S. pombe Chromosomes Enzyme kinetics Gene expression Heterochromatin Methyltransferase Posttranslational modifications Protein complex Ubiquitin Dewey 610 Dewey 615 Dewey 570 Biotechnology and Biological Sciences Research Council BB/S018549 Swiss National Science Foundation Molecular Mechanisms of Centromere Organization 139137 CH Swiss National Science Foundation The nucleosome remodeling and deacetylation complex SHREC 163760 CH Swiss National Science Foundation Nucleosome remodeling, modification and interaction 172904 CH Swiss National Science Foundation How kinases define specificity in lipid signalling? 148269 CH 3 Faculté de médecine 2 7daed2ee-1311-4824-9df9-2e51260a966a Département de biologie moléculaire et cellulaire 16484 31 Section des sciences pharmaceutiques 17 false 443 Biologie d'un parasite intracellulaire obligatoire 773 https://www.rcsb.org/structure/6Z2A eLife 10 695d19fe-1d6f-4eb0-91c5-7a5832891fd2 Article (Published version) Public elife-62682-v1.pdf 6130722 application/pdf CC BY-4.0 3f7069351deeeced5485b3e3052222564dd1edfac6aa72bcd15be960d627f551 640240e6-fe8f-4a67-90f4-2d69e750256c Supplemental data Public elife-62682-supp1-v1-1.docx 8522 application/vnd.openxmlformats-officedocument.wordprocessingml.document d83541f13344921a89d82e8f0c646a033ebcc0f58c783f63aac63355e221eb1a 07f8eca3-51bc-490d-84d8-b6f45fffc0df Supplemental data Public elife-62682-supp2-v1.xlsx 131026 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet d2bc7dd2e9110859bd0e824924417959d5b2f4945f9fe60e9d87b16c9fc083bf 7acb0514-f2ea-4f5b-b33b-362631ff1f63 Supplemental data Public elife-62682-supp3-v1.xlsx 19256 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 2ab5888117985681d1784fc3ef0d0f64675c0119c82fab38c96a4ec1d996dcb9 8bfeb88b-50be-4227-afe3-5accb35b8c0f Supplemental data Public elife-62682-supp4-v1.xlsx 11768 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 26f32ab171e775818b20f30761e3b8aa85a16d79047e3b2e0d40f757a3d8347b 2be15ec1-6eb3-445b-abb2-8d68262063d0 Supplemental data Public elife-62682-figures-v1.pdf 9596932 application/pdf 164a62eec81f54a45ee2498f417e1e43709ba08c0ee9cd9c06b7585ddad2881d openAccess Faculté de médecine Faculté des sciences / Section de biologie / Département de biologie moléculaire et cellulaire Faculté des sciences / Section des sciences pharmaceutiques

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SUV39 SET domains mediate crosstalk of heterochromatic histone marks	eLife	2021	14	190
Epigenetic signalling mechanisms in heterochromatin		2019	1,003	0

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Stirpe, Alessandro