BIOLOGY 3UU3 Chapter Notes - Chapter 2: Hmg-Coa Reductase, Triiodothyronine, Bhlhe41
13 Apr 2017
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A wheel of time: the circadian clock, nuclear receptors, and physiology. Behaviour and physiology of many living organisms exhibit circadian rhythms. Circadian clocks are self-sustained, robust, tunable molecular oscillators; central and peripheral clocks both contain two interlocked transcriptional/post-translational feedback loops, described below: Negative feedback loop: bmal1/clock heterodimers activate transcription of period genes (per1, per2, per3) and cryptochrome genes (cry1, cry2) through e-box cis elements in promoters; per/cry complex then inhibits its own transcription by blocking bmal1-clock activity. Many nuclear receptors exhibit circadian rhythm; some are direct targets of circadian clock; examples in paper: Ppar transcription is induced by bmal1/clock via e-box-rich region; ppar transcription oscillates due to alternating regulation by clock-controlled dbp (activator) and e4bp4 (repressor) Car cycling is regulated by clock-controlled transcription factors (dbf, hlf, tef) Rev-erb circadian clock regulates cyclic expression of hmg-coa reductase and cholesterol 7 - hydroxylase (rate limiting enzymes in cholesterol and bile acid biosynthesis)
