RRC ID 49577
Author Ren B, Tan HL, Nguyen TTT, Sayed AMM, Li Y, Mok YK, Yang H, Chen ES.
Title Regulation of transcriptional silencing and chromodomain protein localization at centromeric heterochromatin by histone H3 tyrosine 41 phosphorylation in fission yeast.
Journal Nucleic Acids Res
Abstract Heterochromatin silencing is critical for genomic integrity and cell survival. It is orchestrated by chromodomain (CD)-containing proteins that bind to methylated histone H3 lysine 9 (H3K9me), a hallmark of heterochromatin. Here, we show that phosphorylation of tyrosine 41 (H3Y41p)-a novel histone H3 modification-participates in the regulation of heterochromatin in fission yeast. We show that a loss-of-function mutant of H3Y41 can suppress heterochromatin de-silencing in the centromere and subtelomere repeat regions, suggesting a de-silencing role for H3Y41p on heterochromatin. Furthermore, we show both in vitro and in vivo that H3Y41p differentially regulates two CD-containing proteins without the change in the level of H3K9 methylation: it promotes the binding of Chp1 to histone H3 and the exclusion of Swi6. H3Y41p is preferentially enriched on centromeric heterochromatin during M- to early S phase, which coincides with the localization switch of Swi6/Chp1. The loss-of-function H3Y41 mutant could suppress the hypersensitivity of the RNAi mutants towards hydroxyurea (HU), which arrests replication in S phase. Overall, we describe H3Y41p as a novel histone modification that differentially regulates heterochromatin silencing in fission yeast via the binding of CD-containing proteins.
Volume 46(1)
Pages 189-202
Published 2018-1-9
DOI 10.1093/nar/gkx1010
PII 4612962
PMID 29136238
PMC PMC5758876
MeSH Cell Cycle Checkpoints / genetics Centromere / genetics* Centromere / metabolism Heterochromatin / genetics* Heterochromatin / metabolism Histones / genetics* Histones / metabolism Loss of Function Mutation Methylation Phosphorylation RNA Interference* S Phase / genetics Schizosaccharomyces / genetics* Schizosaccharomyces / metabolism Schizosaccharomyces pombe Proteins / genetics* Schizosaccharomyces pombe Proteins / metabolism Tyrosine / genetics Tyrosine / metabolism
IF 11.147
Times Cited 2
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