小柯机器人

美国德克萨斯大学西南医学中心Qing Zhang团队近期取得重要工作进展，他们研究发现组蛋白H3第16位脯氨酸羟基化（H3P16oh）修饰调节哺乳动物基因表达。这一研究成果2022年11月8日在线发表于《自然—遗传学》杂志上。

研究人员发现，在哺乳动物细胞中存在一种组蛋白PTM，即组蛋白H3第16位脯氨酸的羟基化（H3P16oh）修饰，由脯氨酸羟化酶EGLN2所催化。H3P16oh通过第4个赖氨酸残基的三甲基化（H3K4me3）增强了KDM5A与其底物组蛋白H3的直接结合，从而增强了KDM5A的染色质募集，并导致靶基因上H3K4me3的相应减少。全基因组和转录组分析表明，EGLN2–KDM5A轴调节哺乳动物细胞中的靶基因表达。

具体而言，这些数据表明，在三阴性乳腺癌（TNBC）中，通过EGLN2-H3P16oh-KDM5A途径抑制WNT通路负调节因子DKK1，可以促进WNT/β-catenin信号传导。这项研究表征了组蛋白编码中的调控标记，并揭示了H3P16oh在调节哺乳动物基因表达中的作用。

据了解，组蛋白翻译后修饰（PTMs）对调节各种DNA模板化过程非常重要。

附：英文原文

Title: Histone H3 proline 16 hydroxylation regulates mammalian gene expression

Author: Liu, Xijuan, Wang, Jun, Boyer, Joshua A., Gong, Weida, Zhao, Shuai, Xie, Ling, Wu, Qiong, Zhang, Cheng, Jain, Kanishk, Guo, Yiran, Rodriguez, Javier, Li, Mingjie, Uryu, Hidetaka, Liao, Chengheng, Hu, Lianxin, Zhou, Jin, Shi, Xiaobing, Tsai, Yi-Hsuan, Yan, Qin, Luo, Weibo, Chen, Xian, Strahl, Brian D., von Kriegsheim, Alex, Zhang, Qi, Wang, Gang Greg, Baldwin, Albert S., Zhang, Qing

Issue&Volume: 2022-11-08

Abstract: Histone post-translational modifications (PTMs) are important for regulating various DNA-templated processes. Here, we report the existence of a histone PTM in mammalian cells, namely histone H3 with hydroxylation of proline at residue 16 (H3P16oh), which is catalyzed by the proline hydroxylase EGLN2. We show that H3P16oh enhances direct binding of KDM5A to its substrate, histone H3 with trimethylation at the fourth lysine residue (H3K4me3), resulting in enhanced chromatin recruitment of KDM5A and a corresponding decrease of H3K4me3 at target genes. Genome- and transcriptome-wide analyses show that the EGLN2–KDM5A axis regulates target gene expression in mammalian cells. Specifically, our data demonstrate repression of the WNT pathway negative regulator DKK1 through the EGLN2-H3P16oh-KDM5A pathway to promote WNT/β-catenin signaling in triple-negative breast cancer (TNBC). This study characterizes a regulatory mark in the histone code and reveals a role for H3P16oh in regulating mammalian gene expression.

DOI: 10.1038/s41588-022-01212-x

Source: https://www.nature.com/articles/s41588-022-01212-x

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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