Journal Article

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

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

2016

Overview

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.

• Publisher: National Academy of Sciences
• Subject: Biological Sciences / Cell Biology / Embryonic growth stage / Estrogens / Eukaryotes / Gene expression / INAUGURAL ARTICLE / Proteins / Ribonucleic acid / RNA / Stem cells