[PDF][PDF] The histone demethylases Jhdm1a/1b enhance somatic cell reprogramming in a vitamin-C-dependent manner

T Wang, K Chen, X Zeng, J Yang, Y Wu, X Shi, B Qin… - Cell stem cell, 2011 - cell.com
T Wang, K Chen, X Zeng, J Yang, Y Wu, X Shi, B Qin, L Zeng, MA Esteban, G Pan, D Pei
Cell stem cell, 2011cell.com
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 …
Summary
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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