Histone Acylation beyond Acetylation: Terra Incognita in Chromatin Biology

Histone acetylation, one of the first and best studied histone post-translational modifications(ptms), as well as the factors involved in its deposition (writers), binding (readers)and removal (erasers), have been shown to act at the heart of regulatory circuits controllingessential cellular functions. the identification of a variety of competing histonelysine-modifying acyl groups including propionyl, butyryl, 2-hydroxyisobutyryl, crotonyl,malonyl, succinyl and glutaryl, raises numerous questions on their functional significance,the molecular systems that manage their establishment, removal and interplay with thewell-known acetylation-based mechanisms. detailed and large-scale investigations of twoof these new histone ptms, crotonylation and 2-hydroxyisobutyrylation, along with histoneacetylation, in the context of male genome programming, where stage-specific geneexpression programs are switched on and off in turn, have shed light on their functionalcontribution to the epigenome for the first time. these initial investigations fired many additionalquestions, which remain to be explored. this review surveys the major results takenfrom these two new histone acylations and discusses the new biology that is emergingbased on the diversity of histone lysine acylations.