P300 Is a preferred client protein for nuclear chaperones (800.6)

Abstract

The KAT3 family of histone acetyl‐transferases, p300 and CBP, are a class of highly versatile epigenetic regulators capable of forming a diverse array of chromatin regulatory complexes that readily adapt to a wide variety of gene promoter contexts to control transcription. These properties require forming multiple conformations through flexible positioning and folding of their various functional domains. Here we show that HSP90 and HSP70 molecular chaperones play a major role in assisting p300/CBP in these molecular functions at gene promoters. Disruption of this chaperone function alters the genome‐wide distribution of p300 and CBP while causing global changes in histone acetylation and gene expression. Major targeted genes include diverse regulators of mammalian protein degradation pathways, thus revealing a previously unrecognized function for molecular chaperones in the epistatic regulation of protein homeostasis through epigenetically regulated transcription of numerous components of protein degradation pathways essential for maintaining protein quality control in the cell.