期刊
CELL STEM CELL
卷 17, 期 6, 页码 689-704出版社
CELL PRESS
DOI: 10.1016/j.stem.2015.09.005
关键词
-
资金
- Catalan Agency for Administration of University and Research (AGAUR) under a Beatriu de Pinos postdoctoral fellowship
- Senior Scholar Award in Aging [AG-SS-2482-10]
- Ellison Medical Foundation
- NIH [HL103967, DA028776, CA154903, GM089778, 1R01-GM095942, P30 NS061777]
- Empire State Stem Cell Fund through the New York State Department of Health (NYSTEM) [C028103, C028121]
Epigenetic and epitranscriptomic networks have important functions in maintaining the pluripotency of embryonic stem cells (ESCs) and somatic cell reprogramming. However, the mechanisms integrating the actions of these distinct networks are only partially understood. Here we show that the chromatin-associated zinc finger protein 217 (ZFP217) coordinates epigenetic and epitranscriptomic regulation. ZFP217 interacts with several epigenetic regulators, activates the transcription of key pluripotency genes, and modulates N6-methyladenosine (m(6)A) deposition on their transcripts by sequestering the enzyme m(6)A methyltransferase-like 3 (METTL3). Consistently, Zfp217 depletion compromises ESC self-renewal and somatic cell reprogramming, globally increases m(6)A RNA levels, and enhances m(6)A modification of the Nanog, Sox2, Klf4, and c-Myc mRNAs, promoting their degradation. ZFP217 binds its own target gene mRNAs, which are also METTL3 associated, and is enriched at promoters of m(6)A-modified transcripts. Collectively, these findings shed light on how a transcription factor can tightly couple gene transcription to m(6)A RNA modification to ensure ESC identity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据