Figure 2. Chromatin Compaction and Histone Modifications Affect Gene Expression.

A. Metabolic cofactors, such as ATP and NADH, work in concert with writers and erasers to orchestrate histone modifications and chromatin condensation. Histone modifications are added by writer, which utilize metabolites as moiety sources (e.g. SAM, Acetyl-CoA and again ATP, and others) to add marks (erasers, accordingly, remove the marks) so that readers, which continuously navigate to and sample histones for proper modifications, can influence gene expression by recruiting transcriptional machinery. B. Rather than a rigid invariant architecture between cells, chromatin organization appears to arise similar to a phase separation, with local regions of accessibility and inaccessibility influenced by protein binding and PTM in response to cell specification cues and environmental stimuli. In this representation, open and active (blue) or closed and inactive (yellow) regions shift in terms of their relative abundance, the features of the domains they occupy and their localization within the nucleus. Chromatin compaction can flow between multiple states, shown here as one with larger more continuous regions of activity or silencing (left) versus smaller more segmented regions of differing accessibility and transcriptional behavior (right).