Identification of a new clock-related element EL-box involved in circadian regulation by BMAL1/CLOCK and HES1
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- 作者：Taichi Ueshima ; Takeshi Kawamoto ; Kiyomasa K. Honda ; Mitsuhide Noshiro ; Katsumi Fujimoto ; Sanae Nakao ; Natsuhiro Ichinose ; Seiichi Hashimoto ; Osamu Gotoh ; Yukio Kato
- 关键词：SCN ; suprachiasmatic nucleus ; RORE ; ROR-responsive element ; ANOVA ; analysis of variance ; LD ; light&ndash ; dark ; DD ; constant darkness ; NC E-box ; noncanonical E-box ; EL ; E-box-like element ; TSS ; transcriptional start site ; TRED ; transcriptional regulatory d
- 刊名：Gene
- 出版年：2012
- 出版时间：1 December, 2012
- 年：2012
- 卷：510
- 期：2
- 页码：118-125
- 全文大小：1196 K
文摘
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¡ä-box. Expression of EL-box-containing genes, including Ank, Dbp, and Nr1d1 (Rev-erb¦Á), 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.