Chromatin-Remodeling Components of the BAF Complex Facilitate Reprogramming

被引:316
作者
Singhal, Nishant [1 ]
Graumann, Johannes [2 ]
Wu, Guangming [1 ]
Arauzo-Bravo, Marcos J. [1 ]
Han, Dong Wook [1 ]
Greber, Boris [1 ]
Gentile, Luca [1 ]
Mann, Matthias [2 ]
Schoeler, Hans R. [1 ,3 ]
机构
[1] Max Planck Inst Mol Biomed, Dept Cell & Dev Biol, D-48149 Munster, Germany
[2] Max Planck Inst Biochem, Dept Prote & Signal Transduct, D-82152 Martinsried, Germany
[3] Univ Munster, Fac Med, D-48149 Munster, Germany
关键词
PLURIPOTENT STEM-CELLS; HUMAN SOMATIC-CELLS; SWI/SNF COMPLEX; GENE-EXPRESSION; SELF-RENEWAL; AMINO-ACIDS; FIBROBLASTS; INDUCTION; REQUIRES; EXTRACT;
D O I
10.1016/j.cell.2010.04.037
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:943 / 955
页数:13
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