The SIN3A/HDAC Corepressor Complex Functionally Cooperates with NANOG to Promote Pluripotency

Cell Reports

Michael H. Reimer, Jr.¹  Carmen Sáenz²  Miguel Fidalgo²  Francesco Faiola²  Dan Li²  Jianlong Wang²  Carlos Sánchez-Priego²  Diana Guallar²  Arven Saunders²  Xin Huang²  Junjun Ding² 

[1] Department of Cell Biology, Neurobiology, and Anatomy, Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53233, USA;The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;

关键词: SIN3A;    HDAC1;    HDAC2;    VPA;    pre-iPSCs;    iPSCs;    EpiSCs;    ESCs;    SIN3B;    TET1/2;   

DOI  :  10.1016/j.celrep.2017.01.055

来源: DOAJ

【 摘 要 】

Although SIN3A is required for the survival of early embryos and embryonic stem cells (ESCs), the role of SIN3A in the maintenance and establishment of pluripotency remains unclear. Here, we find that the SIN3A/HDAC corepressor complex maintains ESC pluripotency and promotes the generation of induced pluripotent stem cells (iPSCs). Members of the SIN3A/HDAC corepressor complex are enriched in an extended NANOG interactome and function in transcriptional coactivation in ESCs. We also identified a critical role for SIN3A and HDAC2 in efficient reprogramming of somatic cells. Mechanistically, NANOG and SIN3A co-occupy transcriptionally active pluripotency genes in ESCs and also co-localize extensively at their genome-wide targets in pre-iPSCs. Additionally, both factors are required to directly induce a synergistic transcriptional program wherein pluripotency genes are activated and reprogramming barrier genes are repressed. Our findings indicate a transcriptional regulatory role for a major HDAC-containing complex in promoting pluripotency.

【 授权许可】

Unknown