Control of embryonic stem cell self-renewal and differentiation via coordinated alternative splicing and translation of YY2

Soroush Tahmasebi, Seyed Mehdi Jafarnejad, Ingrid S. Tam, Thomas Gonatopoulos-Pournatzis, Edna Matta-Camacho, Yoshinori Tsukumo, Akiko Yanagiya, Wencheng Li, Yaser Atlasi, Maxime Caron, Ulrich Braunschweig, Dana Pearl, Arkady Khoutorsky, Christos G. Gkogkas, Robert Nadon, Guillaume Bourque, Xiang Jiao Yang, Bin Tian, Hendrik G. Stunnenberg, Yojiro YamanakaBenjamin J. Blencowe, Vincent Giguère, Nahum Sonenberg

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

47 Citaten (Scopus)

Samenvatting

Translational control of gene expression plays a key role during the early phases of embryonic development. Here we describe a transcriptional regulator of mouse embryonic stem cells (mESCs), Yin-yang 2 (YY2), that is controlled by the translation inhibitors, Eukaryotic initiation factor 4E-binding proteins (4E-BPs). YY2 plays a critical role in regulating mESC functions through control of key pluripotency factors, including Octamer-binding protein 4 (Oct4) and Estrogen-related receptor-β (Esrrb). Importantly, overexpression of YY2 directs the differentiation of mESCs into cardiovascular lineages.We show that the splicing regulator Polypyrimidine tractbinding protein 1 (PTBP1) promotes the retention of an intron in the 5′-UTR of Yy2 mRNA that confers sensitivity to 4E-BP-mediated translational suppression. Thus, we conclude that YY2 is a major regulator of mESC self-renewal and lineage commitment and document a multilayer regulatory mechanism that controls its expression. mRNA translation, 4E-BPs, PTBP, embryonic stem cell, YY2.

Originele taal-2Engels
Pagina's (van-tot)12360-12367
Aantal pagina's8
TijdschriftProceedings of the National Academy of Sciences of the United States of America
Volume113
Nummer van het tijdschrift44
DOI's
StatusGepubliceerd - 1 nov. 2016
Extern gepubliceerdJa

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