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SUV39 SET domains mediate crosstalk of heterochromatic histone marks

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journal contribution
posted on 13.10.2021, 08:56 by Alessandro Stirpe, Nora Guidotti, Sarah J Northall, Sinan Kilic, Alexandre Hainard, Oscar Vadas, Beat Fierz, Thomas Schalch
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.

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (PP00P3_139137); (PP00P3_163760_1); (PP00P3_172904); (PZ00P3_148269)

Biotechnology and Biological Sciences Research Council (BB/S018549)

History

Citation

Stirpe et al. eLife 2021;0:e62682. DOI:https://doi.org/10.7554/eLife.62682

Author affiliation

Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology

Version

VoR (Version of Record)

Published in

ELIFE

Volume

10

Publisher

eLIFE SCIENCES PUBL LTD

issn

2050-084X

eissn

2050-084X

Copyright date

2021

Available date

13/10/2021

Language

English