title: NuRD blocks reprogramming of mouse somatic cells into pluripotent stem cells.
abstract: Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) by overexpression of a defined set of transcription factors requires epigenetic changes in pluripotency genes. Nuclear reprogramming is an inefficient process and the molecular mechanisms that reset the epigenetic state during iPSC generation are largely unknown. Here, we show that downregulation of the nucleosome remodeling and deacetylation (NuRD) complex is required for efficient reprogramming. Overexpression of Mbd3, a subunit of NuRD, inhibits induction of iPSCs by establishing heterochromatic features and silencing embryonic stem cell-specific marker genes, including Oct4 and Nanog. Depletion of Mbd3, on the other hand, improves reprogramming efficiency and facilitates the formation of pluripotent stem cells that are capable of generating viable chimeric mice, even in the absence of c-Myc or Sox2. The results establish Mbd3/NuRD as an important epigenetic regulator that restricts the expression of key pluripotency genes, suggesting that drug-induced downregulation of Mbd3/NuRD may be a powerful means to improve the efficiency and fidelity of reprogramming.
authors.affiliation: Shenzhen Graduate School of Peking University, Shenzhen, China.
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.forename: Te
authors.initials: T
authors.lastname: Ling
authors.forename: Wenbing
authors.initials: W
authors.lastname: Xie
authors.forename: He
authors.initials: H
authors.lastname: Sun
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Qiaoyun
authors.initials: Q
authors.lastname: Zhu
authors.forename: Meili
authors.initials: M
authors.lastname: Shen
authors.forename: Le
authors.initials: L
authors.lastname: Zong
authors.forename: Guoliang
authors.initials: G
authors.lastname: Lyu
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Tao
authors.initials: T
authors.lastname: Ye
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.forename: Wei
authors.initials: W
authors.lastname: Tao
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Lu
authors.forename: Ingrid
authors.initials: I
authors.lastname: Grummt
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D065150:Cellular Reprogramming / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D057890:Epigenomics; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D016259:Genes, myc; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008808:Mice, Inbred CBA; D010957:Plasmids; D011401:Promoter Regions, Genetic; D055748:SOXB1 Transcription Factors / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; C492013:Mbd3 protein, mouse; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex
keywords: Epigenetic regulation; Induced pluripotent stem cells; Mbd3/NuRD; Nanog; Reprogramming efficiency