Intrachromosomal looping is required for activation of endogenous pluripotency genes during reprogramming - PubMed (original) (raw)

doi: 10.1016/j.stem.2013.05.012. Epub 2013 Jun 6.

Weiwei Jiao, Lin Sun, Jiayan Fan, Mengfei Chen, Hong Wang, Xiaoyi Xu, Adong Shen, Tao Li, Beibei Niu, Shengfang Ge, Wei Li, Jiuwei Cui, Guanjun Wang, Jingnan Sun, Xianqun Fan, Xiang Hu, Randall J Mrsny, Andrew R Hoffman, Ji-Fan Hu

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Intrachromosomal looping is required for activation of endogenous pluripotency genes during reprogramming

He Zhang et al. Cell Stem Cell. 2013.

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Abstract

Generation of induced pluripotent stem cells (iPSCs) by defined factors is an extremely inefficient process, because there is a strong epigenetic block preventing cells from achieving pluripotency. Here we report that virally expressed factors bound to the promoters of their target genes to the same extent in both iPSCs and unreprogrammed cells (URCs). However, expression of endogenous pluripotentcy genes was observed only in iPSCs. Comparison of local chromatin structure of the OCT4 locus revealed that there was a cohesin-complex-mediated intrachromosomal loop that juxtaposes a downstream enhancer to the gene's promoter, enabling activation of endogenous stemness genes. None of these long-range interactions were observed in URCs. Knockdown of the cohesin-complex gene SMC1 by RNAi abolished the intrachromosomal interaction and affected pluripotency. These findings highlight the importance of the SMC1-orchestrated intrachromosomal loop as a critical epigenetic barrier to the induction of pluripotency.

Copyright © 2013 Elsevier Inc. All rights reserved.

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