Rhythmic SAF-A binding underlies circadian transcription of the Bmal1 gene.
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.
Onishi
Yoshiaki
Y
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
Hanai
Syuji
S
Ohno
Tomoya
T
Hara
Yasuhiro
Y
Ishida
Norio
N
D024509:3' Flanking Region; D056930:ARNTL Transcription Factors; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D002843:Chromatin / Q000737:chemistry / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology*; D018899:CpG Islands; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D020862:GC Rich Sequence; D017930:Genes, Reporter; D034722:Heterogeneous-Nuclear Ribonucleoprotein U / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D002843:Chromatin; D017931:DNA Primers; D004268:DNA-Binding Proteins; D034722:Heterogeneous-Nuclear Ribonucleoprotein U; D008156:Luciferases; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D020319:Oligodeoxyribonucleotides, Antisense; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; C431792:Arntl2 protein, mouse; C498262:Nr1d1 protein, mouse