title: H2B Tyr37 phosphorylation suppresses expression of replication-dependent core histone genes.
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.
authors.affiliation: Drug Discovery, Moffitt Cancer Center, Tampa, Florida, USA.
authors.forename: Kiran
authors.initials: K
authors.lastname: Mahajan
authors.forename: Bin
authors.initials: B
authors.lastname: Fang
authors.forename: John M
authors.initials: JM
authors.lastname: Koomen
authors.forename: Nupam P
authors.initials: NP
authors.lastname: Mahajan
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D015966:Gene Expression Regulation, Fungal; D056488:Histone Chaperones / Q000378:metabolism; D006657:Histones / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D056488:Histone Chaperones; D006657:Histones; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C081018:histone H2B type 1-A; D014443:Tyrosine; C099685:SWE1 protein, S cerevisiae; D011505:Protein-Tyrosine Kinases; D012319:RNA Polymerase II