- •ZFP217 regulates the expression of the core stem cell gene network
- •ZFP217 is required for efficient somatic cell reprogramming
- •ZFP217 interacts with METTL3 and restrains m6A RNA modification
- •Low m6A levels in ESC-related transcripts enable pluripotency and reprogramming
Coordination of mA mRNA Methylation and Gene Transcription by ZFP217 Regulates Pluripotency and Reprogramming
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 (m6A) deposition on their transcripts by sequestering the enzyme m6A methyltransferase-like 3 (METTL3). Consistently, Zfp217 depletion compromises ESC self-renewal and somatic cell reprogramming, globally increases m6A RNA levels, and enhances m6A 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 m6A-modified transcripts. Collectively, these findings shed light on how a transcription factor can tightly couple gene transcription to m6A RNA modification to ensure ESC identity.
To access this article, please choose from the options below
Purchase access to this article
You must be logged in to purchase this article.
If you are a current subscriber with Society Membership or an Account Number, claim your access now.
Subscribe to this title
Purchase a subscription to gain access to this and all other articles in this journal.
Visit ScienceDirect to see if you have access via your institution.