PMID:18243098

Citation	Shimada, M, Niida, H, Zineldeen, DH, Tagami, H, Tanaka, M, Saito, H and Nakanishi, M (2008) Chk1 is a histone H3 threonine 11 kinase that regulates DNA damage-induced transcriptional repression. Cell 132:221-32
Abstract	DNA damage results in activation or suppression of transcription of a large number of genes. Transcriptional activation has been well characterized in the context of sequence-specific DNA-bound activators, whereas mechanisms of transcriptional suppression are largely unexplored. We show here that DNA damage rapidly reduces histone H3 Threonine 11 (T11) phosphorylation. This correlates with repression of genes, including cyclin B1 and cdk1. H3-T11 phosphorylation occurs throughout the cell cycle and is Chk1 dependent in vivo. Following DNA damage, Chk1 undergoes rapid chromatin dissociation, concomitant with reduced H3-T11 phosphorylation. Furthermore, we find that loss of H3-T11 phosphorylation correlates with reduced binding of the histone acetyltransferase GCN5 at cyclin B1 and cdk1 promoters and reduced H3-K9 acetylation. We propose a mechanism for Chk1 as a histone kinase, responsible for DNA-damage-induced transcriptional repression by loss of histone acetylation.
Links	PubMed Online version:10.1016/j.cell.2007.12.013
Keywords	Adenoviridae/genetics; Animals; Cells, Cultured; Culture Media, Serum-Free; DNA Damage; Embryo, Mammalian; Fibroblasts/metabolism; Fibroblasts/radiation effects; Gene Expression Regulation; HCT116 Cells; Histones/genetics; Histones/metabolism; Humans; Mice; Models, Genetic; Phosphorylation/radiation effects; Protein Kinases/analysis; Protein Kinases/chemistry; Protein Kinases/genetics; Protein Kinases/metabolism; Protein Kinases/physiology; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; Substrate Specificity; Transcription, Genetic; Ultraviolet Rays
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:CHK1	enables	GO:0035402: histone kinase activity (H3-T11 specific)	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
MOUSE:CHK1	part_of	GO:0000785: chromatin	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:CHK1	involved_in	GO:2000615: regulation of histone H3-K9 acetylation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:CHK1	involved_in	GO:0048096: chromatin-mediated maintenance of transcription	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:CHK1	involved_in	GO:0010767: regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:CHK1	enables	GO:0035402: histone kinase activity (H3-T11 specific)	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete

References

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