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.
Bibliographical noteFunding Information:
This work was funded by grants from the NIH (CA-31534, NHARP-003658-0149), Cancer Prevention Research Institute (CPRIT RP100612), and the Maria Betzner Morrow Endowment to H.T. and by an Oklahoma Center for Adult Stem Cell Research award to C.F.W. M.P. is a CPRIT scholar (CPRIT RP101501). We thank Chhaya Das, June Harriss, Maya Ghosh, Amrita Das, Charles Martin, Hongxia Liu, and Stephen Chiang for technical assistance and Jonghwan Kim for discussion and critical reading of the manuscript. We thank the CPRIT Core Facility Support group (CPRIT-RP120348) for assistance with ChIP sequencing library and sequencing.