title: The SIN3A/HDAC Corepressor Complex Functionally Cooperates with NANOG to Promote Pluripotency.
abstract: 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.
authors.affiliation: The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Arven
authors.initials: A
authors.lastname: Saunders
authors.affiliation: The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Fidalgo
authors.affiliation: Department of Cell Biology, Neurobiology, and Anatomy, Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53233, USA; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Reimer
authors.affiliation: The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Faiola
authors.affiliation: The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Junjun
authors.initials: J
authors.lastname: Ding
authors.affiliation: The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Sánchez-Priego
authors.affiliation: The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Guallar
authors.affiliation: The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Sáenz
authors.affiliation: The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: jianlong.wang@mssm.edu.
authors.forename: Jianlong
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming / Q000235:genetics / Q000502:physiology; D056970:Co-Repressor Proteins / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005801:Genes, Homeobox / Q000235:genetics; D016678:Genome / Q000235:genetics; D056464:Histone Deacetylase 2 / Q000378:metabolism*; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D000071317:Nanog Homeobox Protein / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D056970:Co-Repressor Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D012097:Repressor Proteins; C099683:SIN3A transcription factor; C533424:Hdac2 protein, mouse; D056464:Histone Deacetylase 2; D056264:Sin3 Histone Deacetylase and Corepressor Complex
keywords: ESCs; EpiSCs; HDAC1; HDAC2; SIN3A; SIN3B; TET1/2; VPA; iPSCs; pre-iPSCs