Functional analysis of DEC2 and its role in chondrogenic differentiation

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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