Summary The transcriptional coactivator p300 is a histone lysine acetyltransferase that is typically recruited to transcriptional enhancers and regulates gene expression by acetylating chromatin. Here we show that p300 activation directly depends on the activation and oligomerisation status of transcription factor (TF) ligands. Using two model TFs, IRF3 and STAT1, we demonstrate that TF dimerization enables trans-autoacetylation of p300 in a highly conserved and intrinsically disordered autoinhibitory lysine-rich loop (AIL), resulting in HAT activation. We describe a p300 crystal structure in which the AIL invades the active site of a neighbouring HAT domain thus revealing a snap-shot of a trans-autoacetylation reaction intermediate. Substrate access to the active site involves rearrangement of an autoinhibitory RING domain. Our data explain how cellular signalling, TF activation and dimerization controls p300 activation thus explaining why gene transcription is associated with chromatin acetylation.
Prior to its transmission to the offspring, the male genome has to be tightly compacted. A genome-scale histone eviction and the subsequent repackaging of DNA by protamines (Prms) direct this essential genome condensation step. The requirement for male germ cells to undergo such a dramatic and unique genome reorganization explains why these cells express the largest number of histone variants, including many testis-specific ones. Indeed, an open chromatin, nucleosome instability and a facilitated process of histone disassembly are direct consequences of the presence of these histone variants in the chromatin of male germ cells. These histone-induced changes in chromatin first control a stage-specific gene expression program and then directly mediate the histone-to-Prm transition process. This review aims at summarizing and discussing a series of recent functional studies of male germ cell histone variants with a focus on their impact on the process of histone eviction and male genome compaction.
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