Histone H4 acetylation at lysine 16 (H4K16ac) is a unique histone modification that plays a significant role in the regulation of chromatin structure and gene expression. This modification is catalyzed by the enzyme MOF (MYST-family lysine acetyltransferase), which is evolutionarily conserved and has been implicated in a variety of cellular processes, including the regulation of metabolism, cell cycle control, and cellular responses to DNA damage. It is the only known acetylation mark that is maintained across generations, suggesting its importance in epigenetic inheritance and gene regulation. In the context of metabolism, H4K16ac has been linked to the control of central carbon metabolism and diet-induced obesity in mice. Mice with reduced levels of MOF, the enzyme responsible for H4K16ac, show altered glucose assimilation, impaired insulin response, and resistance to weight gain when fed a high-fat diet. This is associated with changes in the transcriptional regulation of genes involved in glucose uptake and lipid storage in white adipose tissue. Moreover, H4K16ac has been implicated in the regulation of mitochondrial function and ciliary biogenesis.
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