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Molecular and Cellular Biology, May 2008, p. 3477-3488, Vol. 28, No. 10
0270-7306/08/$08.00+0     doi:10.1128/MCB.02227-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Rhythmic SAF-A Binding Underlies Circadian Transcription of the Bmal1 Gene{triangledown}

Yoshiaki Onishi,1* Syuji Hanai,1 Tomoya Ohno,1,2 Yasuhiro Hara,1,2 and Norio Ishida1,2*

Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba 305-8566, Japan,1 Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8576, Japan2

Received 16 December 2007/ Returned for modification 6 February 2008/ Accepted 29 February 2008

Although Bmal1 is a key component of the mammalian clock system, little is understood about the actual mechanism of circadian Bmal1 gene transcription, particularly at the chromatin level. Here we discovered a unique chromatin structure within the Bmal1 promoter. The RORE region, which is a critical cis element for the circadian regulation of the Bmal1 gene, is comprised of GC-rich open chromatin. The 3'-flanking region of the promoter inhibited rhythmic transcription in the reporter gene assay in vitro even in the presence of ROR{alpha} and REV-ERB{alpha}. We also found that the nuclear matrix protein SAF-A binds to the 3'-flanking region with circadian timing, which was correlated with Bmal1 expression by footprinting in vivo. These results suggest that the unique chromatin structure containing SAF-A is required for the circadian transcriptional regulation of the Bmal1 gene in cells.

* Corresponding author. Mailing address: Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan. Phone: 81-29-861-6053. Fax: 81-29-861-9499. E-mail for Yoshiaki Onishi: y-onishi{at}aist.go.jp. E-mail for Norio Ishida: n.ishida{at}aist.go.jp

{triangledown} Published ahead of print on 10 March 2008.

Molecular and Cellular Biology, May 2008, p. 3477-3488, Vol. 28, No. 10
0270-7306/08/$08.00+0     doi:10.1128/MCB.02227-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hara, Y., Onishi, Y., Oishi, K., Miyazaki, K., Fukamizu, A., Ishida, N. (2009). Molecular characterization of Mybbp1a as a co-repressor on the Period2 promoter. Nucleic Acids Res 37: 1115-1126 [Abstract] [Full Text]  


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