来自吉林大学的胡继繁(Ji-Fan Hu)教授、上海交通大学的范先群(Xianqun Fan)教授以及斯坦福大学大学医学院的Andrew R. Hoffman为这篇论文的共同通讯作者。胡继繁教授曾在肿瘤和干细胞表观遗传学研究领域取得诸多原创性成果,发表SCI源刊论著40余篇。范先群教授主攻眼部肿瘤和眼眶外科,在基础研究和临床治疗方面取得突出成就,在国内外眼科杂志发表学术论文110余篇。
Intrachromosomal Looping Is Required for Activation of Endogenous Pluripotency Genes during Reprogramming
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 genes 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.