Document Detail

Histone H3K27me3 demethylases KDM6A and KDM6B modulate definitive endoderm differentiation from human ESCs by regulating WNT signaling pathway.
MedLine Citation:
PMID:  22907667     Owner:  NLM     Status:  MEDLINE    
Definitive endoderm differentiation is crucial for generating respiratory and gastrointestinal organs including pancreas and liver. However, whether epigenetic regulation contributes to this process is unknown. Here, we show that the H3K27me3 demethylases KDM6A and KDM6B play an important role in endoderm differentiation from human ESCs. Knockdown of KDM6A or KDM6B impairs endoderm differentiation, which can be rescued by sequential treatment with WNT agonist and antagonist. KDM6A and KDM6B contribute to the activation of WNT3 and DKK1 at different differentiation stages when WNT3 and DKK1 are required for mesendoderm and definitive endoderm differentiation, respectively. Our study not only uncovers an important role of the H3K27me3 demethylases in definitive endoderm differentiation, but also reveals that they achieve this through modulating the WNT signaling pathway.
Wei Jiang; Jinzhao Wang; Yi Zhang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-08-21
Journal Detail:
Title:  Cell research     Volume:  23     ISSN:  1748-7838     ISO Abbreviation:  Cell Res.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-03     Completed Date:  2013-06-18     Revised Date:  2014-01-10    
Medline Journal Info:
Nlm Unique ID:  9425763     Medline TA:  Cell Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  122-30     Citation Subset:  IM    
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MeSH Terms
Cell Differentiation
Cell Line
Embryonic Stem Cells / cytology,  metabolism*
Endoderm / cytology*,  metabolism
Histone Demethylases / antagonists & inhibitors,  genetics,  metabolism*
Histones / genetics,  metabolism
Intercellular Signaling Peptides and Proteins / metabolism
Jumonji Domain-Containing Histone Demethylases / antagonists & inhibitors,  genetics,  metabolism*
Nuclear Proteins / antagonists & inhibitors,  genetics,  metabolism*
RNA Interference
RNA, Small Interfering / metabolism
Wnt Signaling Pathway
Wnt3 Protein / agonists,  antagonists & inhibitors,  metabolism*
Grant Support
Reg. No./Substance:
0/DKK1 protein, human; 0/Histones; 0/Intercellular Signaling Peptides and Proteins; 0/Nuclear Proteins; 0/RNA, Small Interfering; 0/Wnt3 Protein; EC 1.14.11.-/Histone Demethylases; EC 1.14.11.-/Jumonji Domain-Containing Histone Demethylases; EC 1.14.11.-/KDM6B protein, human; EC 1.14.11.-/UTX protein, human

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