SUV39 SET domains mediate crosstalk of heterochromatic histone marks

Alessandro Stirpe, Nora Guidotti, Sarah J. Northall, Sinan Kilic, Alexandre Hainard, Oscar Vadas, Beat Fierz, Thomas Schalch*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

15 Citationer (Scopus)
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Abstract

Y 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.

OriginalsprogEngelsk
Artikelnummer62682
TidsskrifteLife
Vol/bind10
Antal sider26
ISSN2050-084X
DOI
StatusUdgivet - 2021
Udgivet eksterntJa

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