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

First Author  Tahmasebi S Year  2016
Journal  Proc Natl Acad Sci U S A Volume  113
Issue  44 Pages  12360-12367
PubMed ID  27791185 Mgi Jnum  J:238787
Mgi Id  MGI:5824161 Doi  10.1073/pnas.1615540113
Citation  Tahmasebi S, et al. (2016) Control of embryonic stem cell self-renewal and differentiation via coordinated alternative splicing and translation of YY2. Proc Natl Acad Sci U S A 113(44):12360-12367
abstractText  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-beta (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.
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