Vertebrate-like CRYPTOCHROME 2 from monarch regulates circadian transcription via independent repression of CLOCK and BMAL1 activity

作者：Ying Zhang, Matthew J. Markert, Shayna C. Groves, Paul E. Hardin, Christine Merlin · 发表于：Proceedings of the National Academy of Sciences · 年份：2017 · DOI：10.1073/pnas.1702014114 · 被引用次数：82 · 研究领域：Circadian rhythm and melatonin、Light effects on plants、Genetics, Aging, and Longevity in Model Organisms

Significance Daily rhythms in animal behavior, physiology, and metabolism are driven by cell-autonomous mechanisms that keep time and control overt rhythms via transcriptional feedback loops, making it fundamental to define the mechanisms driving rhythmic transcription. In mammals, PERIOD and CRYPTOCHROME (CRY) rhythmically repress CLOCK:BMAL1 transcriptional activity, but the mechanisms by which CRY represses CLOCK:BMAL1 activity are not fully understood. Using CRISPR/Cas9 for in vivo genetic manipulations in the monarch, we show that repression of circadian transcription by vertebrate-like CRY is mediated primarily by a BMAL1 transactivation domain (TAD)-independent mechanism involving the CLK-PAS B domain, while repression on the BMAL1 TAD is dispensable for the generation of rhythms but alters circadian phase during the first day of constant darkness by affecting activation levels.