TY - JOUR
T1 - Control of embryonic stem cell self-renewal and differentiation via coordinated alternative splicing and translation of YY2
AU - Tahmasebi, Soroush
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 G.
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
N1 - Funding Information:
We thank Martin Klar, Tommy Alain, Joshua Dunn, Jelena Popic, and Ola Larsson for discussions; Serge Gueroussov, Bushra Raj, and Vinagolu Rajasekhar for reagents; Joseph Marcotrigiano for the HEK293H cell line; and Annie Sylvestre and Annik Lafrance for animal care. This work was supported by Canadian Institutes of Health Research CIHR Grants MOP-142200 (to N.S.), MOP-125885 (to V.G.), MOP-115090 (to G.B.), MOP-111197 (to Y.Y.), and MOP-14609 (to B.J.B.). S.M.J. is the recipient of a CIHR Postdoctoral fellowship. S.T. is the recipient of a Richard and Edith Strauss fellowship. U.B. is the recipient of a Human Frontier Science Program Long Term Fellowship. T.G.-P. was supported by an EMBO (European Molecular Biology Organization) Fellowship and an Ontario Institute for Regenerative Medicine Fellowship.
PY - 2016/11/1
Y1 - 2016/11/1
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 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.
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 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.
UR - http://www.scopus.com/inward/record.url?scp=84994037267&partnerID=8YFLogxK
U2 - 10.1073/pnas.1615540113
DO - 10.1073/pnas.1615540113
M3 - Article
C2 - 27791185
AN - SCOPUS:84994037267
SN - 0027-8424
VL - 113
SP - 12360
EP - 12367
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 44
ER -