By J. G. Reich, E. Selkov
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WDR5 was identified as a PER1-interacting protein, and it also binds to PER2 (Brown et al. 2005). WDR5 is part of a histone methyltransferase complex and is important for H3K4 trimethylation and H3K9 dimethylation at the Rev-erb-α promoter (Brown et al. 2005). Reducing WDR5 levels reduces histone methylation at PER1-regulated promoters, but does not alter circadian period length (Brown et al. 2005). A histone lysine demethylase JARID1a (Jumonji, AT-rich interactive domain 1a, also called lysine (K)-specific demethylase 5A, or KDM5A) activates CLOCK– BMAL1 activity and influences circadian clock function (DiTacchio et al.
Weaver The Methamphetamine-Sensitive Circadian Oscillator Another SCN-independent oscillator that shares many properties with the FEO is the methamphetamine-sensitive circadian oscillator (MASCO), initially identified by Sato and Ken-Ichi Honma and colleagues (Honma et al. 1987). Allowing SCN-lesioned, arrhythmic rats to drink water containing a low concentration of methamphetamine led to restoration of robust locomotor activity rhythms with a period length of ~26 h. To rule out the possibility that this rhythmic behavior was due to rhythmicity in drug intake, additional studies were conducted in which methamphetamine was administered by mini-osmotic pumps, with similar results (Honma et al.
2014). PGC1-α and PPAR-γ also provide molecular links between circadian clocks and metabolism (Liu et al. 2007b). A more extensive discussion of the interface between circadian clocks and metabolism appears in Chap. 5 by C. B. Green. (See also Peek et al. 3 Histone Methylation In the Dbp gene, circadian rhythms of H3K9 acetylation and dimethylation peak in opposite phases, with the peak in acetylation occurring coincident with transcription and the peak of dimethylation occurring during the repression phase of the circadian cycle (Ripperger and Schibler 2006).
