TY - JOUR
T1 - Control of embryonic stem cells self-renewal and differentiation via coordinated splicing and translation of YY2
AU - Tahmasebi, Soroush Tahmasebi
AU - Jafarnejad, Seyed Mehdi
AU - Tam, Ingrid S.
AU - Gonatopoulos-Pournatzis, Thomas
AU - Matta-Camacho, Edna
AU - Tsukumo, Yoshinori
AU - Yanagiya, Akiko
AU - Li, Wencheng
AU - Atlasi, Yaser
AU - Caron, Maxime
AU - Braunschweig, Ulrich
AU - Pearl, Dana
AU - Khoutorsky, Arkady
AU - Gkogkas, Christos
AU - Nadon, Robert
AU - Bourque, Guillaume
AU - Yang, Xiang-Jiao
AU - Tian, Bin
AU - Stunnenberg, Hendrik G.
AU - Yamanaka, Yojiro
AU - Blencowe, Benjamin J.
AU - Giguère, Vincent
AU - Sonenberg, Nahum
PY - 2016/11
Y1 - 2016/11
N2 - 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.
AB - 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.
U2 - 10.1073/pnas.1615540113
DO - 10.1073/pnas.1615540113
M3 - Article
C2 - 27791185
SN - 0027-8424
SP - 12360
EP - 12367
JO - Proceedings of the National Academy of Sciences (PNAS)
JF - Proceedings of the National Academy of Sciences (PNAS)
ER -