title: Knockdown of Brm and Baf170, Components of Chromatin Remodeling Complex, Facilitates Reprogramming of Somatic Cells.
abstract: The SWI/SNF (SWItch/Sucrose NonFermentable or BAF, Brg/Brahma-associated factors) complexes are epigenetic modifiers of chromatin structure and undergo progressive changes in subunit composition during cellular differentiation. For example, in embryonic stem cells, esBAF contains Brg1 and Baf155, while their homologs, Brm and Baf170, are present in BAF of somatic cells. In this study, we sought to determine whether Brm and Baf170 play any roles in induced pluripotent stem cell (iPSC) reprogramming by using shRNA-mediated knockdown studies in the mouse model. We found that knocking down Brm during early, mid, and late stages (days 3, 6, and 9 after initial iPSC induction) and knocking down Baf170 during late-stage (day 9) reprogramming improve the numbers of iPSC colonies formed. We further showed that inhibition of these somatic BAF components also promotes complete reprogramming of partially reprogrammed somatic cells (pre-iPSCs). Finally, we found that the expression of Brm and Baf170 during reprogramming was regulated by Jak/Stat3 activity. Taken together, these data suggest that inhibiting somatic BAF improves complete reprogramming by facilitating the activation of the pluripotency circuitry.
authors.affiliation: 1 Department of Animal Science, Center for Regenerative Biology, University of Connecticut , Storrs, Connecticut.
authors.forename: Zongliang
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: 1 Department of Animal Science, Center for Regenerative Biology, University of Connecticut , Storrs, Connecticut.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: 1 Department of Animal Science, Center for Regenerative Biology, University of Connecticut , Storrs, Connecticut.
authors.forename: Xueming
authors.initials: X
authors.lastname: Zhao
authors.affiliation: 1 Department of Animal Science, Center for Regenerative Biology, University of Connecticut , Storrs, Connecticut.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: 2 Animal Biosciences and Biotechnology Laboratory, Agricultural Research Services , United States Department of Agriculture, Beltsville, Maryland.
authors.forename: David M
authors.initials: DM
authors.lastname: Donovan
authors.affiliation: 1 Department of Animal Science, Center for Regenerative Biology, University of Connecticut , Storrs, Connecticut.
authors.forename: Xiuchun Cindy
authors.initials: XC
authors.lastname: Tian
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D055748:SOXB1 Transcription Factors; C499503:Smarca2 protein, mouse; C587872:Smarcc2 protein, mouse; C527783:Sox2 protein, mouse; D014157:Transcription Factors