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Publication : A genome-wide RNAi screen identifies opposing functions of Snai1 and Snai2 on the Nanog dependency in reprogramming.

First Author  Gingold JA Year  2014
Journal  Mol Cell Volume  56
Issue  1 Pages  140-52
PubMed ID  25240402 Mgi Jnum  J:215538
Mgi Id  MGI:5605602 Doi  10.1016/j.molcel.2014.08.014
Citation  Gingold JA, et al. (2014) A genome-wide RNAi screen identifies opposing functions of Snai1 and Snai2 on the Nanog dependency in reprogramming. Mol Cell 56(1):140-52
abstractText  Nanog facilitates embryonic stem cell self-renewal and induced pluripotent stem cell generation during the final stage of reprogramming. From a genome-wide small interfering RNA screen using a Nanog-GFP reporter line, we discovered opposing effects of Snai1 and Snai2 depletion on Nanog promoter activity. We further discovered mutually repressive expression profiles and opposing functions of Snai1 and Snai2 during Nanog-driven reprogramming. We found that Snai1, but not Snai2, is both a transcriptional target and protein partner of Nanog in reprogramming. Ectopic expression of Snai1 or depletion of Snai2 greatly facilitates Nanog-driven reprogramming. Snai1 (but not Snai2) and Nanog cobind to and transcriptionally activate pluripotency-associated genes including Lin28 and miR-290-295. Ectopic expression of miR-290-295 cluster genes partially rescues reprogramming inefficiency caused by Snai1 depletion. Our study thus uncovers the interplay between Nanog and mesenchymal factors Snai1 and Snai2 in the transcriptional regulation of pluripotency-associated genes and miRNAs during the Nanog-driven reprogramming process.
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