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Histone crotonylation regulates neural stem cell fate decisions by activating bivalent promoters
EMBO Reports ( IF 7.7 ) Pub Date : 2021-08-09 , DOI: 10.15252/embr.202052023
Shang-Kun Dai 1, 2, 3 , Pei-Pei Liu 1, 3 , Hong-Zhen Du 1, 3 , Xiao Liu 1, 2, 3 , Ya-Jie Xu 1, 2, 3 , Cong Liu 1, 2, 3 , Ying-Ying Wang 1, 2, 3 , Zhao-Qian Teng 1, 2, 3, 4 , Chang-Mei Liu 1, 2, 3, 4
Affiliation  

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.

中文翻译:

组蛋白巴豆酰化通过激活二价启动子调节神经干细胞命运决定

组蛋白赖氨酸巴豆酰化 (Kcr) 是一种进化上保守且广泛存在的非乙酰短链赖氨酸酰化,在转录调控和疾病过程中起重要作用。然而,在发育过程中,组蛋白 Kcr 的全基因组分布、动态变化以及与基因表达的关联在很大程度上是未知的。在本研究中,我们发现组蛋白 Kcr 主要位于活性启动子区域,作为高表达基因的表观遗传标志,并调节参与代谢和增殖的基因。此外,升高的组蛋白 Kcr 激活二价启动子,通过增加染色质开放性和 RNA 聚合酶 II (RNAP2) 的募集来刺激神经干/祖细胞 (NSPC) 中的基因表达。在功能上,这些激活的基因有助于转录组重塑并促进神经元分化。总体而言,组蛋白 Kcr 标记具有高基因表达的活性启动子,并修改局部染色质环境以允许基因激活。
更新日期:2021-10-06
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