The Ink4/Arf locus is a barrier for iPS cell reprogramming.

ABSTRACT: The mechanisms involved in the reprogramming of differentiated cells into induced pluripotent stem (iPS) cells by the three transcription factors Oct4 (also known as Pou5f1), Klf4 and Sox2 remain poorly understood. The Ink4/Arf locus comprises the Cdkn2a-Cdkn2b genes encoding three potent tumour suppressors, namely p16(Ink4a), p19(Arf) and p15(Ink4b), which are basally expressed in differentiated cells and upregulated by aberrant mitogenic signals. Here we show that the locus is completely silenced in iPS cells, as well as in embryonic stem (ES) cells, acquiring the epigenetic marks of a bivalent chromatin domain, and retaining the ability to be reactivated after differentiation. Cell culture conditions during reprogramming enhance the expression of the Ink4/Arf locus, further highlighting

SUBMITTER: Li H 

PROVIDER: S-EPMC3578184 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature