组蛋白
抄写(语言学)
基因
赖氨酸
细胞生物学
遗传学
转录因子
基因表达调控
生物
计算生物学
氨基酸
语言学
哲学
作者
Ziru Niu,Chen Chen,Siyu Wang,Congcong Lu,Zhiyue Wu,Aiyuan Wang,Jing Mo,Jianji Zhang,Yanpu Han,Yuan Yuan,Yingao Zhang,Yong Zang,Chaofan He,Xue Bai,Shanshan Tian,Guijin Zhai,Xudong Wu,Kai Zhang
标识
DOI:10.1038/s41467-024-47900-6
摘要
Lysine lactylation (Kla) links metabolism and gene regulation and plays a key role in multiple biological processes. However, the regulatory mechanism and functional consequence of Kla remain to be explored. Here, we report that HBO1 functions as a lysine lactyltransferase to regulate transcription. We show that HBO1 catalyzes the addition of Kla in vitro and intracellularly, and E508 is a key site for the lactyltransferase activity of HBO1. Quantitative proteomic analysis further reveals 95 endogenous Kla sites targeted by HBO1, with the majority located on histones. Using site-specific antibodies, we find that HBO1 may preferentially catalyze histone H3K9la and scaffold proteins including JADE1 and BRPF2 can promote the enzymatic activity for histone Kla. Notably, CUT&Tag assays demonstrate that HBO1 is required for histone H3K9la on transcription start sites (TSSs). Besides, the regulated Kla can promote key signaling pathways and tumorigenesis, which is further supported by evaluating the malignant behaviors of HBO1- knockout (KO) tumor cells, as well as the level of histone H3K9la in clinical tissues. Our study reveals HBO1 serves as a lactyltransferase to mediate a histone Kla-dependent gene transcription.
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