H2B Tyr37 phosphorylation suppresses expression of replication-dependent core histone genes

Kiran Mahajan, Bin Fang, John M. Koomen, Nupam P. Mahajan

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Histone gene transcription is actively downregulated after completion of DNA synthesis to avoid overproduction. However, the precise mechanistic details of the cessation of histone mRNA synthesis are not clear. We found that histone H2B phosphorylation at Tyr37 occurs upstream of histone cluster 1, Hist1, during the late S phase. We identified WEE1 as the kinase that phosphorylates H2B at Tyr37. Loss of expression or inhibition of WEE1 kinase abrogated H2B Tyr37 phosphorylation with a concomitant increase in histone transcription in yeast and mammalian cells. H2B Tyr37 phosphorylation excluded binding of the transcriptional coactivator NPAT and RNA polymerase II and recruited the histone chaperone HIRA upstream of the Hist1 cluster. Taken together, our data show a previously unknown and evolutionarily conserved function for WEE1 kinase as an epigenetic modulator that marks chromatin with H2B Tyr37 phosphorylation, thereby inhibiting the transcription of multiple histone genes to lower the burden on the histone mRNA turnover machinery.

Original languageEnglish
Pages (from-to)930-937
Number of pages8
JournalNature Structural and Molecular Biology
Volume19
Issue number9
DOIs
StatePublished - Sep 1 2012
Externally publishedYes

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