BMAL1 (ARNTL), CLOCK, and NPAS2 are basic helix-loop-helix transcription factors. In humans BMAL1 has been demonstrated to form a heterodimer with CLOCK. In mouse, BMAL1 can form a heterodimer with either CLOCK or NPAS2. By analogy with other basic helix-loop-helix proteins the basic domain binds DNA, in this case the E-box motif, and the helix-loop-helix domains interact to form the heterodimer. BMAL1 and CLOCK/NPAS2 are codependently phosphorylated by unknown kinases after dimerization. The phosphorylation enhances transactivation activity and is inhibited by PER:CRY complexes. Both CLOCK and NPAS2 are expressed in the suprachiasmatic nucleus of the hypothalamus and act redundantly there. The tissue distributions of CLOCK and NPAS2 do not entirely overlap, however. For example, NPAS2 but not CLOCK is found in forebrain.
Dudley, C, Garcia, JA, Reick, M, McKnight, SL
Rutter, J, Reick, M, Wu, LC, McKnight, SL
Jain, S, Hogenesch, JB, Gu, YZ, Bradfield, CA
King, DP, Nguyen, HB, Weitz, CJ, Takahashi, JS, Staknis, D, Gekakis, N, Davis, FC, Wilsbacher, LD
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