Chromatin-Remodeling Components of the BAF Complex Facilitate Reprogramming.
Reprogramming of somatic cells achieved by combination of the four transcription factors Oct4, Sox2, Klf4, and c-Myc has very low efficiency. To increase the reprogramming efficiency and better understand the process, we sought to identify factors that mediate reprogramming with higher efficiency. We established an assay to screen nuclear fractions from extracts of pluripotent mouse cells based on Oct4 reactivation. Using proteomics, we identified components of the ATP-dependent BAF chromatin-remodeling complex, which significantly increases reprogramming efficiency when used together with the four factors. The reprogrammed cells could transmit to the germline and exhibited pluripotency. Reprogramming remained highly efficient when c-Myc was not present but BAF components were overexpressed. BAF complex components mediate this effect by facilitating enhanced Oct4 binding to target promoters during reprogramming. Thus, somatic cell reprogramming using chromatin-remodeling molecules represents an efficient method of generating reprogrammed cells.
Singhal
Nishant
N
Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, D-48149 Münster, Germany.
Graumann
Johannes
J
Wu
Guangming
G
Araúzo-Bravo
Marcos J
MJ
Han
Dong Wook
DW
Greber
Boris
B
Gentile
Luca
L
Mann
Matthias
M
Schöler
Hans R
HR
D000818:Animals; D002460:Cell Line; D065150:Cellular Reprogramming; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D000090062:Kruppel-Like Factor 4; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D002843:Chromatin; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; C491090:Smarcc1 protein, mouse; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases