Tyrosine phosphorylation of histone H2A by CK2 regulates transcriptional elongation
Post-translational histone modifications have a critical role in regulating transcription, the cell cycle, DNA replication andDNA damage repair1 . The identification of new histone modifications critical for transcriptional regulation at initiation, elongation or termination is of particular interest. Here we report a new layer of regulation in transcriptional elongation that is conserved from yeast to mammals. This regulation is based on the phosphorylation of a highly conserved tyrosine residue, Tyr 57, in histone H2A and is mediated by the unsuspected tyrosine kinase activity of casein kinase 2 (CK2). Mutation of Tyr 57 in H2Ain yeast or inhibition of CK2 activityimpairs transcriptional elongation in yeast as well asin mammalian cells. Genome-wide binding analysis reveals that CK2a, the catalytic subunit of CK2, binds across RNA-polymerase-II-transcribed coding genes and active enhancers.Mutation of Tyr 57 causes a loss of H2Bmono-ubiquitination as well as H3K4me3 and H3K79me3, histone marks associated with active transcription. Mechanistically, both CK2 inhibition and the H2A(Y57F) mutation enhance H2B deubiquitination activity of the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, suggesting a critical role of this phosphorylation in coordinating the activity of the SAGA complex during transcription. Together, these resultsidentify a new component of regulation in transcriptional elongation based onCK2-dependent tyrosine phosphorylation of the globular domain of H2A.