Functional analysis of DEC2 and its role in chondrogenic differentiation

DEC2是一种基本的螺旋-环-螺旋(BHLH)蛋白，与Hair、Hes和Hey相关，它们都参与组织发育。DEC2的转录本在视交叉上核表现出明显的昼夜振荡，这表明DEC2是钟表系统的调节蛋白。1.DEC2蛋白与CACGTG E-box序列结合并抑制CACGTG元件转录的功能分析。此外，DEC2通过抑制MyoD/E47异二聚化抑制MyoD介导的反式激活。2.DEC2基因表达的调节作为核心昼夜节律环路的正成分Clock/BMAL异源二聚体上调DEC2mRNA的表达。与野生型小鼠肾脏的振荡模式相反，时钟/时钟突变小鼠的DEC2mRNA水平非常低，昼夜节律表达被取消。荧光素酶分析表明，Clock/BMAL通过与DEC2启动子上的CACGTG E-box相互作用来调控DEC2基因的表达。此外，DEC2通过与E-box结合来抑制自身的表达。因此，DEC2的转录受CLOCK/BMAL的正调控，而受DEC2通过共同的CACGTG E-box负调控

DEC2 is a basic helix-loop-helix (bHLH) protein related to hairy, Hes, and Hey, which are known to be involved in tissue development. Transcripts of DEC2 exhibit a striking circadian oscillation in the suprachiasmatic nucleus, suggesting that DEC2 functions as regulatory protein for the clockwork system1.Functional analysis of DEC2 proteinDEC2 bound to CACGTG E-box sequences and repressed transcription from the CACGTG elements. In addition, DEC2 repressed MyoD-mediated transactivation by inhibiting of MyoD/E47 heterodimerization2.Regulation of DEC2 gene expressionClock/Bmal heterodimer, which acts as positive component in a core circadian loop, up-regulated expression of DEC2 mRNA. In contrast to the oscillation pattern seem in the kidneys of wild-type mice, DEC2 mRNA levels were very low and the circadian expressions were abolished in Clock/Clock mutant mice. Luciferase assays showed Clock/Bmal regulate DEC2 gene expression through interactions with CACGTG E-boxes in the DEC2 promoter. In addition, DEC2 repressed its own expression through binding to the E-boxes. Thus, transcription of DEC2 was positively regulated by Clock/Bmal and negatively regulated by DEC2 via the common CACGTG E-boxes