Journal
CELL STEM CELL
Volume 9, Issue 6, Pages 575-587Publisher
CELL PRESS
DOI: 10.1016/j.stem.2011.10.005
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Funding
- Ministry of Science and Technology [2009CB941102, 2011CB965200, 2011CBA01106]
- Chinese Academy of Sciences [XDA01020401, XDA01020106, XDA01020202, XDA01020404]
- National Natural Science Foundation of China [90813033]
- National S&T Major Special Project on Major New Drug Innovation [2011ZX09102-010]
- Bureau of Science and Technology of Guangzhou Municipality [2010U1-E00521]
- Chinese Academy of Sciences/SAFEA
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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.
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