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Molecular and Cellular Biology, July 2004, p. 6278-6287, Vol. 24, No. 14
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.14.6278-6287.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Circadian and Light-Induced Transcription of Clock Gene Per1 Depends on Histone Acetylation and Deacetylation

Yoshihisa Naruse, Kentaro Oh-hashi, Norio Iijima, Midori Naruse, Hideyo Yoshioka, and Masaki Tanaka*

Department of Anatomy, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-0841, Japan

Received 8 September 2003/ Returned for modification 21 November 2003/ Accepted 16 April 2004

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.

* Corresponding author. Mailing address: Department of Anatomy, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-0841, Japan. Phone: 81-75-251-5302. Fax: 81-75-251-5304. E-mail: mtanaka{at}koto.kpu-m.ac.jp.

Molecular and Cellular Biology, July 2004, p. 6278-6287, Vol. 24, No. 14
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.14.6278-6287.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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