The Sin3a/HDAC co-repressor complex cooperates with Nanog in promoting stem cell pluripotency and somatic cell reprogramming [Microarray Expression]

Despite the requirement of Sin3a for survival of early embryos and embryonic stem cells (ESCs), mechanistic action of Sin3a in the maintenance and establishment of pluripotency remains unexplored. Here we report the transcriptional regulatory roles of Sin3a in maintaining ESC pluripotency and in reprogramming somatic cells towards full pluripotency. Sin3a/HDAC complex members were enriched in an extended Nanog interactome and exhibited a predominant transcriptional co-activator role at a global level in ESCs. We also established a critical role for Sin3a in efficient reprogramming of somatic cells towards full pluripotency. Nanog and Sin3a co-localize at almost all of their genome-wide targets in pre-iPSCs, and both factors are required to directly induce a synergistic transcriptional program wherein pluripotency genes are activated and reprogramming barrier genes are repressed. Our results, for the first time, establish positive roles of the Sin3a/HDAC complex in the maintenance and establishment of pluripotency.

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Saunders A, Huang X, Fidalgo M, Reimer MH Jr, Faiola F, Ding J, Sánchez-Priego C, Guallar D, Sáenz C, Li D, Wang J