Histone crotonylation regulates neural stem cell fate decisions by activating bivalent promoters

Abstract

Histone lysine crotonylation (Kcr), an evolutionarily conserved and widespread non-acetyl short-chain lysine acylation, plays important roles in transcriptional regulation and disease processes. However, the genome-wide distribution, dynamic changes, and associations with gene expression of histone Kcr during developmental processes are largely unknown. In this study, we find that histone Kcr is mainly located in active promoter regions, acts as an epigenetic hallmark of highly expressed genes, and regulates genes participating in metabolism and proliferation. Moreover, elevated histone Kcr activates bivalent promoters to stimulate gene expression in neural stem/progenitor cells (NSPCs) by increasing chromatin openness and recruitment of RNA polymerase II (RNAP2). Functionally, these activated genes contribute to transcriptome remodeling and promote neuronal differentiation. Overall, histone Kcr marks active promoters with high gene expression and modifies the local chromatin environment to allow gene activation.

The role of histone modifications: from neurodevelopment to neurodiseases

“…Elevated histone Kcr promotes NSC/NPC cell fate decision and accompanies embryonic neurogenesis. 135 …”

Acylations in cardiovascular biology and diseases, what's beyond acetylation

“…For instance, the low endogenous level of benzoylation makes it difficult to study their functions in cardiovascular biology. 39 Besides, the established ChIP-grade anti-histone crotonylation antibodies do not work well for ChIP-seq analysis, 32 , 94 and ChIP-grade antibodies for many types of histone acylations (such as site-specific benzoylation antibodies) have not been developed. It is difficult to identify specific PTM residues that are crucial for cardiovascular physiology and pathology in vivo because of the fast-changing nature of some types of modifications such as O-GlcNAcylation.…”

The crosstalking of lactate‐Histone lactylation and tumor

“…As a target for HIV [130] 6. Maintenance of telomeres and stem cell differentiation [131] Prostate cancer [132] Colorectal cancer [133] Liver cancer [134] Leukemia [135] Succinylation (Ksucc) Succinyl-CoA; Succinate 1. Stimulate gene transcription [136] 2.…”