Rhythmic SAF-A binding underlies circadian transcription of the Bmal1 gene

Yoshiaki Onishi; Syuji Hanai; Tomoya Ohno; Yasuhiro Hara; Norio Ishida

doi:10.1128/MCB.02227-07

Rhythmic SAF-A binding underlies circadian transcription of the Bmal1 gene

Mol Cell Biol. 2008 May;28(10):3477-88. doi: 10.1128/MCB.02227-07. Epub 2008 Mar 10.

Authors

Yoshiaki Onishi¹, Syuji Hanai, Tomoya Ohno, Yasuhiro Hara, Norio Ishida

Affiliation

¹ Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan. y-onishi@aist.go.jp

Abstract

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 RORalpha and REV-ERBalpha. 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3' Flanking Region
ARNTL Transcription Factors
Animals
Base Sequence
Basic Helix-Loop-Helix Transcription Factors / genetics*
Binding Sites / genetics
Chromatin / chemistry
Chromatin / genetics
Circadian Rhythm / genetics*
Circadian Rhythm / physiology*
CpG Islands
DNA Primers / genetics
DNA-Binding Proteins / metabolism
GC Rich Sequence
Genes, Reporter
Heterogeneous-Nuclear Ribonucleoprotein U / metabolism*
Luciferases / genetics
Mice
Molecular Sequence Data
NIH 3T3 Cells
Nuclear Receptor Subfamily 1, Group D, Member 1
Nuclear Receptor Subfamily 1, Group F, Member 1
Oligodeoxyribonucleotides, Antisense / genetics
Promoter Regions, Genetic
Protein Binding
Receptors, Cytoplasmic and Nuclear / metabolism
Trans-Activators / metabolism
Transcription, Genetic

Substances

ARNTL Transcription Factors
Arntl2 protein, mouse
Basic Helix-Loop-Helix Transcription Factors
Chromatin
DNA Primers
DNA-Binding Proteins
Heterogeneous-Nuclear Ribonucleoprotein U
Nr1d1 protein, mouse
Nuclear Receptor Subfamily 1, Group D, Member 1
Nuclear Receptor Subfamily 1, Group F, Member 1
Oligodeoxyribonucleotides, Antisense
Receptors, Cytoplasmic and Nuclear
Trans-Activators
Luciferases