title: Identification of a new clock-related element EL-box involved in circadian regulation by BMAL1/CLOCK and HES1.
abstract: Several cis-acting elements play critical roles in maintaining circadian expression of clock and clock-controlled genes. Using in silico analysis, we identified 10 sequence motifs that are correlated with the circadian phases of gene expression in the cartilage. One of these motifs, an E-box-like clock-related element (EL-box; GGCACGAGGC), can mediate BMAL1/CLOCK-induced transcription, which is typically regulated through an E-box or E'-box. Expression of EL-box-containing genes, including Ank, Dbp, and Nr1d1 (Rev-erbα), was induced by BMAL1/CLOCK or BMAL1/NPAS2. Compared with the E-box, the EL-box elements had distinct responsiveness to DEC1, DEC2, and HES1: suppressive actions of DEC1 and DEC2 on the EL-box were less potent than those on the E-box. HES1, which is known to bind to the N-box (CACNAG), suppressed enhancer activity of the EL-box, but not the E-box. In the Dbp promoter, an EL-box worked cooperatively with a noncanonical (NC) E-box to mediate BMAL1/CLOCK actions. These findings suggest that in addition to known clock elements, the EL-box element may contribute to circadian regulation of clock and clock-controlled genes.
authors.affiliation: Department of Dental and Medical Biochemistry, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima 734-8553, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Ueshima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Kiyomasa K
authors.initials: KK
authors.lastname: Honda
authors.forename: Mitsuhide
authors.initials: M
authors.lastname: Noshiro
authors.forename: Katsumi
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Sanae
authors.initials: S
authors.lastname: Nakao
authors.forename: Natsuhiro
authors.initials: N
authors.lastname: Ichinose
authors.forename: Seiichi
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Osamu
authors.initials: O
authors.lastname: Gotoh
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
mesh_terms: D056930:ARNTL Transcription Factors / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D056926:CLOCK Proteins / Q000378:metabolism*; D002356:Cartilage / Q000378:metabolism*; D057906:Circadian Clocks; D016384:Consensus Sequence; D006132:Growth Plate / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D050436:Regulatory Elements, Transcriptional; D000072056:Transcription Factor HES-1; D059467:Transcriptome
chemical_list: D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D018398:Homeodomain Proteins; D000072056:Transcription Factor HES-1; C489735:Hes1 protein, rat; C538945:Clock protein, rat