Chunk #26 — Epigenetics-Relevant Consequences of Oxidative Alcohol Metabolism — Increases in NADH/NAD+ Ratio and Their Consequences — Modulation of Gene Expression
PER2, PER3) genes. PER and CRY proteins bind to CLOCK/BMAL1 and inhibit their transcriptional activity (Bass and Takahashi 2010). Furthermore, using the nuclear receptor REV-ERB as a feedback loop, BMAL1 drives the transcription of Rev-erbα, which in turn inhibits Bmal1 transcription (Preitner et al. 2002). In addition, the retinoid-related orphan receptors (RORα, β, γ) activate BMAL1 and REV-ERBα (Jetten 2009). Misalignment of these activities with the internal clock disrupts energy homeostasis and could result in metabolic diseases, such as those observed in shift workers (Wang et al. 2011).
