Bright/Arid3A Acts as a Barrier to Somatic Cell Reprogramming through Direct Regulation of Oct4, Sox2, and Nanog

摘要

Summary We show here that singular loss of the Bright/Arid3A transcription factor leads to reprograming of mouse embryonic fibroblasts (MEFs) and enhancement of standard four-factor (4F) reprogramming. Bright-deficient {MEFs} bypass senescence and, under standard embryonic stem cell (ESC) culture conditions, spontaneously form clones that in?vitro express pluripotency markers, differentiate to all germ lineages, and in?vivo form teratomas and chimeric mice. We demonstrate that {BRIGHT} binds directly to the promoter/enhancer regions of Oct4, Sox2, and Nanog to contribute to their repression in both {MEFs} and ESCs. Thus, elimination of the {BRIGHT} barrier may provide an approach for somatic cell reprogramming.