title: Tyrosine phosphorylation of histone H2A by CK2 regulates transcriptional elongation.
abstract: Post-translational histone modifications have a critical role in regulating transcription, the cell cycle, DNA replication and DNA damage repair. 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 H2A in yeast or inhibition of CK2 activity impairs transcriptional elongation in yeast as well as in mammalian cells. Genome-wide binding analysis reveals that CK2α, the catalytic subunit of CK2, binds across RNA-polymerase-II-transcribed coding genes and active enhancers. Mutation of Tyr 57 causes a loss of H2B mono-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 results identify a new component of regulation in transcriptional elongation based on CK2-dependent tyrosine phosphorylation of the globular domain of H2A.
authors.affiliation: 1] Howard Hughes Medical Institute, Department of Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Biomedical Sciences Graduate Program, School of Medicine, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Harihar
authors.initials: H
authors.lastname: Basnet
authors.affiliation: Division of Biological Sciences, Section of Molecular Biology, UCSD Moores Cancer Center, University of California San Diego, La Jolla, California 92093-0347, USA.
authors.forename: Xue B
authors.initials: XB
authors.lastname: Su
authors.affiliation: Howard Hughes Medical Institute, Department of Medicine, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Meisenhelder
authors.affiliation: 1] Howard Hughes Medical Institute, Department of Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Bioinformatics and Systems Biology Program, Department of Bioengineering, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Daria
authors.initials: D
authors.lastname: Merkurjev
authors.affiliation: Howard Hughes Medical Institute, Department of Medicine, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Ohgi
authors.affiliation: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Hunter
authors.affiliation: Division of Biological Sciences, Section of Molecular Biology, UCSD Moores Cancer Center, University of California San Diego, La Jolla, California 92093-0347, USA.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Pillus
authors.affiliation: Howard Hughes Medical Institute, Department of Medicine, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenfeld
mesh_terms: D000595:Amino Acid Sequence; D047390:Casein Kinase II / Q000378:metabolism*; D002460:Cell Line; D017124:Conserved Sequence; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D061805:Transcription Elongation, Genetic; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism*; D054875:Ubiquitination / Q000235:genetics
chemical_list: D006657:Histones; D014443:Tyrosine; D047390:Casein Kinase II