| Literature DB >> 27791185 |
Soroush Tahmasebi1,2, Seyed Mehdi Jafarnejad1,2, Ingrid S Tam1,2, Thomas Gonatopoulos-Pournatzis3, Edna Matta-Camacho1,2, Yoshinori Tsukumo1,2, Akiko Yanagiya1,2, Wencheng Li4, Yaser Atlasi5, Maxime Caron6,7, Ulrich Braunschweig3, Dana Pearl1,2, Arkady Khoutorsky8, Christos G Gkogkas9, Robert Nadon6,7, Guillaume Bourque6,7, Xiang-Jiao Yang1,2,10, Bin Tian4, Hendrik G Stunnenberg5, Yojiro Yamanaka1,6, Benjamin J Blencowe3,11, Vincent Giguère1,2,10, Nahum Sonenberg12,3.
Abstract
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 tract-binding 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.Entities:
Keywords: 4E-BPs; PTBP; YY2; embryonic stem cell; mRNA translation
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Year: 2016 PMID： 27791185 PMCID： PMC5098618 DOI： 10.1073/pnas.1615540113
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205