-acetyltransferase NAT10 Controls Cell Fates Via Connecting MRNA Cytidine Acetylation to Chromatin Signaling

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2024 Jan 12

PMID 38215194

Authors

Zhensheng Hu

Yunkun Lu

Jie Cao

Lianyu Lin

Xi Chen

Ziyu Zhou

Jiaqi Pu

Guo Chen

Xiaojie Ma

Qian Deng

Yan Jin

Liling Jiang

Yuhan Li

Tengwei Li

Jianzhao Liu

Saiyong Zhu

Affiliations

Soon will be listed here.

Abstract

Cell fate transition involves dynamic changes of gene regulatory network and chromatin landscape, requiring multiple levels of regulation, yet the cross-talk between epitranscriptomic modification and chromatin signaling remains largely unknown. Here, we uncover that suppression of -acetyltransferase 10 (NAT10), the writer for mRNA -acetylcytidine (acC) modification, can notably affect human embryonic stem cell (hESC) lineage differentiation and pluripotent reprogramming. With integrative analysis, we identify that NAT10-mediated acC modification regulates the protein levels of a subset of its targets, which are strongly enriched for fate-instructive chromatin regulators, and among them, histone chaperone ANP32B is experimentally verified and functionally relevant. Furthermore, NAT10-acC-ANP32B axis can modulate the chromatin landscape of their downstream genes (e.g., key regulators of Wnt and TGFβ pathways). Collectively, we show that NAT10 is an essential regulator of cellular plasticity, and its catalyzed mRNA cytidine acetylation represents a critical layer of epitranscriptomic modulation and uncover a previously unrecognized, direct cross-talk between epitranscriptomic modification and chromatin signaling during cell fate transitions.

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