Dynamic Opposition of Histone Modifications

Gene transcription does not only require writers of active histone modifications; on-site opposition by erasers is essential for many genes. Here, we propose the concept of dynamic opposition of histone modifications to explain this conundrum. We highlight the requirement of HDACs for acetylation balance at superenhancers, and the requirement of KDM5A for H4K3me3 recycling at highly active gene promoters. We propose that histone post-translational modifications regulate charge balance for biomolecular condensate formation and nucleosome turnover and form a short-term memory that informs lock-and-step checkpoints for chromatin engagement by RNA polymerase II.