Metabolites regulating chromatin accessibility: a piece of the puzzle

Graphical AbstractThe binding of DNA to histone proteins can be regulated by modifications to the histone tail (e.g. methylation, acetylation, lactylation), which in turn result in different stretches of the chromatin becoming accessible. This allows for the transcription of different genes and, subsequently, for the execution of different cellular functions. It remains largely unexplored, whether and when chaperones assist in the modification of histone tails by 'writers' or 'erasers' during ASCVD. Further open questions concern the mode of modification, e.g. whether modifying enzymes act directly on the assembled nucleosome or on histone dimers, requiring histone exchange or nucleosome (re-)assembly. The availability of substrates, chaperones and modifying enzymes, as well as enzyme activity, could potentially be affected by the tissue/cell type, pathophysiological context, e.g. whether hypoxia is a physiological or pathological situation for the cell type/tissue of interest, as well as by potential compensatory mechanisms. In response to an acute challenge, differences might be observed in a time-dependent manner.Open in new tabDownload slide