Document Detail


The SMAD2/3 corepressor SNON maintains pluripotency through selective repression of mesendodermal genes in human ES cells.
MedLine Citation:
PMID:  23154981     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Activin/Nodal signaling via SMAD2/3 maintains human embryonic stem cell (hESC) pluripotency by direct transcriptional regulation of NANOG or, alternatively, induces mesoderm and definitive endoderm (DE) formation. In search of an explanation for these contrasting effects, we focused on SNON (SKIL), a potent SMAD2/3 corepressor that is expressed in hESCs but rapidly down-regulated upon differentiation. We show that SNON predominantly associates with SMAD2 at the promoters of primitive streak (PS) and early DE marker genes. Knockdown of SNON results in premature activation of PS and DE genes and loss of hESC morphology. In contrast, enforced SNON expression inhibits DE formation and diverts hESCs toward an extraembryonic fate. Thus, our findings provide novel mechanistic insight into how a single signaling pathway both regulates pluripotency and directs lineage commitment.
Authors:
Norihiro Tsuneyoshi; Ee Kim Tan; Akila Sadasivam; Yogavalli Poobalan; Tomoyuki Sumi; Norio Nakatsuji; Hirofumi Suemori; N Ray Dunn
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Genes & development     Volume:  26     ISSN:  1549-5477     ISO Abbreviation:  Genes Dev.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-16     Completed Date:  2013-01-17     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2471-6     Citation Subset:  IM    
Affiliation:
Institute of Medical Biology, A*STAR (Agency for Science, Technology, and Research), Singapore, Singapore.
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MeSH Terms
Descriptor/Qualifier:
Cell Differentiation / genetics
Cell Line
Co-Repressor Proteins / genetics,  metabolism
Embryonic Stem Cells / metabolism*
Gene Expression Regulation, Developmental*
Gene Knockdown Techniques
Humans
Intracellular Signaling Peptides and Proteins / genetics*,  metabolism*
Mesoderm / metabolism
Pluripotent Stem Cells / metabolism*
Proto-Oncogene Proteins / genetics*,  metabolism*
Signal Transduction
Smad2 Protein / genetics,  metabolism*
Smad3 Protein / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Co-Repressor Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/Proto-Oncogene Proteins; 0/SKIL protein, human; 0/Smad2 Protein; 0/Smad3 Protein
Comments/Corrections

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