Histone lysine crotonylation regulates cell-fate determination of neural stem/progenitor cells by activating bivalent promoters

Abstract

Histone lysine crotonylation (Kcr), an evolutionarily conserved and widely expressed non-acetyl short-chain lysine acylation, plays important roles in transcriptional regulation and disease development. However, its genome-wide distribution, correlation with gene expression, and dynamic changes during developmental processes are largely unknown. In this study, we find that histone Kcr is mainly distributed in active promoters, has a ge-nome-wide positive correlation with transcriptional activity, and regulates transcription of genes participating in metabolism and proliferation. Moreover, elevated histone Kcr activates bivalent promoters to stimulate gene expression in neural stem/progenitor cells (NSPCs), through increasing chromatin openness and recruitment of RNA polymerase II (Pol II). Functionally, these activated genes remodel transcriptome and promote neuronal differentiation. Author summaryOverall, histone Kcr marks active promoters with high gene expression and modifies the local chromatin environment to allow gene activation, which influences neuronal cell fate. It may represent a unique active histone mark involved in neural developmental regulation.