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. Author manuscript; available in PMC: 2021 Sep 28.
Published in final edited form as: Trends Biochem Sci. 2020 May 6;45(9):731–747. doi: 10.1016/j.tibs.2020.04.002

Figure 5: Known and Proposed Effects of NAD+, FAD, and SAM availability on chromatin structure and function.

Figure 5:

Circadian rhythm and dietary intake affect cellular availability of key metabolites that act as cofactors for chromatin modifying enzymes such as NAD+, FAD, and SAM. (A) Fluctuations in NAD+ levels enable SIRT1-dependent regulation of CLOCK target genes (e.g. NAMPT) through 2 independent yet non-exclusive mechanisms: 1) histone/BMAL1 deacetylation and 2) deacetylation of the CLOCK:BMAL1 negative regulator PER2. (B) Changes in SAM and FAD availability have been shown to directly influence chromatin methylation states, although the effect of circadian fluctuations in the abundances of these cofactors is unknown. Interestingly, the literature suggests methyl-modifications at certain loci are more sensitive (highlighted in yellow) to altered SAM and FAD availability than other loci (highlighted in blue). This mechanism may allow for dynamic flexibility in chromatin structure and function by enabling cells to adapt to various perturbations, while still supporting critical chromatin functions.