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The Histone Demethylases Jhdm1a/1b Enhance Somatic Cell Reprogramming in a Vitamin-C-Dependent Manner.
MedLine Citation:
PMID:  22100412     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) resets the epigenome to an embryonic-like state. Vitamin C enhances the reprogramming process, but the underlying mechanisms are unclear. Here we show that the histone demethylases Jhdm1a/1b are key effectors of somatic cell reprogramming downstream of vitamin C. We first observed that vitamin C induces H3K36me2/3 demethylation in mouse embryonic fibroblasts in culture and during reprogramming. We then identified Jhdm1a/1b, two known vitamin-C-dependent H3K36 demethylases, as potent regulators of reprogramming through gain- and loss-of-function approaches. Furthermore, we found that Jhdm1b accelerates cell cycle progression and suppresses cell senescence during reprogramming by repressing the Ink4/Arf locus. Jhdm1b also cooperates with Oct4 to activate the microRNA cluster 302/367, an integral component of the pluripotency machinery. Our results therefore reveal a role for H3K36me2/3 in cell fate determination and establish a link between histone demethylases and vitamin-C-induced reprogramming.
Authors:
Tao Wang; Keshi Chen; Xiaoming Zeng; Jianguo Yang; Yun Wu; Xi Shi; Baoming Qin; Lingwen Zeng; Miguel Angel Esteban; Guangjin Pan; Duanqing Pei
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-17
Journal Detail:
Title:  Cell stem cell     Volume:  -     ISSN:  1875-9777     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101311472     Medline TA:  Cell Stem Cell     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
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