Regulation of the circadian clock by the metabolic enzyme AHCY

Mammalian circadian rhythms are based on coupled transcriptional-translational feedback loops driven by the transcription factors CLOCK and BMAL1. Chromatin remodeling mechanisms are essential for the proper timing and extent of circadian gene expression. We report that the S-adenosylhomocysteine (SAH) hydrolysing enzyme AHCY binds to CLOCK-BMAL1 at chromatin and drives circadian transcription by promoting cyclic H3K4 trimethylation and recruitment of BMAL1 to chromatin. H3K4me3 and BMAL1 ChIP-seq in mouse embryonic fibroblasts (MEF) synchronized with dexamethasone and treated with a specific inhibitor for AHCY (DZnep). ChIP was performed at circadian time (CT) 12 and CT24.