Circadian and light-induced transcription of clock gene Per1 depends on histone acetylation and deacetylation.
Circadian clock genes are regulated through a transcriptional-translational feedback loop. Alterations of the chromatin structure by histone acetyltransferases and histone deacetylases (HDACs) are commonly implicated in the regulation of gene transcription. However, little is known about the transcriptional regulation of mammalian clock genes by chromatin modification. Here, we show that the state of acetylated histones fluctuated in parallel with the rhythm of mouse Per1 (mPer1) or mPer2 expression in fibroblast cells and liver. Mouse CRY1 (mCRY1) repressed transcription with HDACs and mSin3B, which was relieved by the HDAC inhibitor trichostatin A (TSA). In turn, TSA induced endogenous mPer1 expression as well as the acetylation of histones H3 and H4, which interacted with the mPer1 promoter region in fibroblast cells. Moreover, a light pulse stimulated rapid histone acetylation associated with the promoters of mPer1 or mPer2 in the suprachiasmatic nucleus (SCN) and the binding of phospho-CREB in the CRE of mPer1. We also showed that TSA administration into the lateral ventricle induced mPer1 and mPer2 expression in the SCN. Taken together, these data indicate that the rhythmic transcription and light induction of clock genes are regulated by histone acetylation and deacetylation.
Naruse
Yoshihisa
Y
Department of Anatomy, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-0841, Japan.
Oh-hashi
Kentaro
K
Iijima
Norio
N
Naruse
Midori
M
Yoshioka
Hideyo
H
Tanaka
Masaki
M
D000107:Acetylation; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D018797:Cell Cycle Proteins; D002843:Chromatin / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D056931:Cryptochromes; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000378:metabolism; D008027:Light; D008099:Liver / Q000166:cytology / Q000502:physiology; D046911:Macromolecular Substances; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D056950:Period Circadian Proteins; D017956:Photoreceptor Cells, Invertebrate; D011401:Promoter Regions, Genetic; D011500:Protein Synthesis Inhibitors / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D012097:Repressor Proteins / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D018797:Cell Cycle Proteins; D002843:Chromatin; C538964:Cry1 protein, mouse; D056931:Cryptochromes; D017362:Cyclic AMP Response Element-Binding Protein; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D046911:Macromolecular Substances; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D011500:Protein Synthesis Inhibitors; D043562:Receptors, G-Protein-Coupled; D012097:Repressor Proteins; C115812:Sin3b protein, mouse; D014157:Transcription Factors; C119828:cry protein, Drosophila; C012589:trichostatin A; D006655:Histone Deacetylases