Phosphorylation of histone H2A inhibits transcription on chromatin templates.
The regulation of gene expression via the histone code has, for the most part, revealed that histone modifications cause the recruitment of adaptor proteins that indirectly regulate the synthesis of RNA. Using purified factors to assemble and modify the chromatin and to transcribe the DNA, we investigated whether modifications of histones may directly impact the RNA polymerase II transcription process. We screened proteins known to modify histones for effects on transcription, and we found that the mitogen- and stress-induced kinase, MSK1, inhibited RNA synthesis. Inhibition of transcription by MSK1 was most sensitive when the template was in chromatin, as naked DNA templates were resistant to the effects of MSK1. We found that MSK1 phosphorylated histone H2A on serine 1, and mutation of serine 1 to alanine blocked the inhibition of transcription by MSK1. Furthermore, we found that acetylation of histone H3 by the p300 and CREB-binding protein associated factor, PCAF, suppressed the kinase-dependent inhibition of transcription. These results suggest that acetylation of histones may stimulate transcription by suppressing an inhibitory phosphorylation by a kinase as MSK1.
Zhang
Ye
Y
Department of Pathology, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Griffin
Karen
K
Mondal
Neelima
N
Parvin
Jeffrey D
JD
D002843:Chromatin / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism*; D012694:Serine / Q000737:chemistry / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D002843:Chromatin; D006657:Histones; D011994:Recombinant Proteins; D012694:Serine; D012313:RNA; D004247:DNA; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1; D012319:RNA Polymerase II