SUV39 SET domains mediate crosstalk of heterochromatic histone marks

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 methyltrans...

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Autores principales:	Alessandro Stirpe, Nora Guidotti, Sarah J Northall, Sinan Kilic, Alexandre Hainard, Oscar Vadas, Beat Fierz, Thomas Schalch
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	heterochromatin methyltransferase ubiquitin posttranslational modifications enzyme kinetics protein complex Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/9fce28dce8f64cc388467c3c13dde5f4
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id	oai:doaj.org-article:9fce28dce8f64cc388467c3c13dde5f4
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spelling	oai:doaj.org-article:9fce28dce8f64cc388467c3c13dde5f42021-11-24T12:14:36ZSUV39 SET domains mediate crosstalk of heterochromatic histone marks10.7554/eLife.626822050-084Xe62682https://doaj.org/article/9fce28dce8f64cc388467c3c13dde5f42021-09-01T00:00:00Zhttps://elifesciences.org/articles/62682https://doaj.org/toc/2050-084XThe 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 Schizosaccharomyces pombe, 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 clr4 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.Alessandro StirpeNora GuidottiSarah J NorthallSinan KilicAlexandre HainardOscar VadasBeat FierzThomas SchalcheLife Sciences Publications Ltdarticleheterochromatinmethyltransferaseubiquitinposttranslational modificationsenzyme kineticsprotein complexMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	heterochromatin methyltransferase ubiquitin posttranslational modifications enzyme kinetics protein complex Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	heterochromatin methyltransferase ubiquitin posttranslational modifications enzyme kinetics protein complex Medicine R Science Q Biology (General) QH301-705.5 Alessandro Stirpe Nora Guidotti Sarah J Northall Sinan Kilic Alexandre Hainard Oscar Vadas Beat Fierz Thomas Schalch SUV39 SET domains mediate crosstalk of heterochromatic histone marks
description	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 Schizosaccharomyces pombe, 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 clr4 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.
format	article
author	Alessandro Stirpe Nora Guidotti Sarah J Northall Sinan Kilic Alexandre Hainard Oscar Vadas Beat Fierz Thomas Schalch
author_facet	Alessandro Stirpe Nora Guidotti Sarah J Northall Sinan Kilic Alexandre Hainard Oscar Vadas Beat Fierz Thomas Schalch
author_sort	Alessandro Stirpe
title	SUV39 SET domains mediate crosstalk of heterochromatic histone marks
title_short	SUV39 SET domains mediate crosstalk of heterochromatic histone marks
title_full	SUV39 SET domains mediate crosstalk of heterochromatic histone marks
title_fullStr	SUV39 SET domains mediate crosstalk of heterochromatic histone marks
title_full_unstemmed	SUV39 SET domains mediate crosstalk of heterochromatic histone marks
title_sort	suv39 set domains mediate crosstalk of heterochromatic histone marks
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/9fce28dce8f64cc388467c3c13dde5f4
work_keys_str_mv	AT alessandrostirpe suv39setdomainsmediatecrosstalkofheterochromatichistonemarks AT noraguidotti suv39setdomainsmediatecrosstalkofheterochromatichistonemarks AT sarahjnorthall suv39setdomainsmediatecrosstalkofheterochromatichistonemarks AT sinankilic suv39setdomainsmediatecrosstalkofheterochromatichistonemarks AT alexandrehainard suv39setdomainsmediatecrosstalkofheterochromatichistonemarks AT oscarvadas suv39setdomainsmediatecrosstalkofheterochromatichistonemarks AT beatfierz suv39setdomainsmediatecrosstalkofheterochromatichistonemarks AT thomasschalch suv39setdomainsmediatecrosstalkofheterochromatichistonemarks
_version_	1718415063521427456

SUV39 SET domains mediate crosstalk of heterochromatic histone marks

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