An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming

被引：295

作者：

Gabut, Mathieu ^{[1
,2
]}

Samavarchi-Tehrani, Payman ^{[3
,5
]}

Wang, Xinchen ^{[1
,2
]}

Slobodeniuc, Valentina ^{[1
,2
]}

O'Hanlon, Dave ^{[1
,2
]}

Sung, Hoon-Ki ^{[4
]}

Alvarez, Manuel ^{[2
,6
]}

Talukder, Shaheynoor ^{[1
,2
]}

Pan, Qun ^{[1
,2
]}

Mazzoni, Esteban O. ^{[7
]}

Nedelec, Stephane ^{[7
]}

Wichterle, Hynek ^{[7
]}

Woltjen, Knut ^{[4
]}

Hughes, Timothy R. ^{[1
,2
]}

Zandstra, Peter W. ^{[2
,6
]}

Nagy, Andras ^{[4
,5
]}

Wrana, Jeffrey L. ^{[3
,5
]}

Blencowe, Benjamin J. ^{[1
,2
,5
]}

机构：

[1] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5S 3E1, Canada

[2] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada

[3] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ctr Syst Biol, Toronto, ON M5G 1X5, Canada

[4] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ctr Stem Cells & Tissue Engn, Toronto, ON M5G 1X5, Canada

[5] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada

[6] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON M5T 1P7, Canada

[7] Columbia Univ, Med Ctr, New York, NY 10032 USA

来源：

CELL | 2011年 / 147卷 / 01期

关键词：

DNA-BINDING; TRANSCRIPTIONAL NETWORK; SEQUENCE SPECIFICITY; FOXP1; DIFFERENTIATION; PROLIFERATION; MICROARRAY; COMPLEXITY; DROSOPHILA; DIVERSITY;

D O I：

10.1016/j.cell.2011.08.023

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：

Alternative splicing (AS) is a key process underlying the expansion of proteomic diversity and the regulation of gene expression. Here, we identify an evolutionarily conserved embryonic stem cell (ESC)-specific AS event that changes the DNA-binding preference of the forkhead family transcription factor FOXP1. We show that the ESC-specific isoform of FOXP1 stimulates the expression of transcription factor genes required for pluripotency, including OCT4, NANOG, NR5A2, and GDF3, while concomitantly repressing genes required for ESC differentiation. This isoform also promotes the maintenance of ESC pluripotency and contributes to efficient reprogramming of somatic cells into induced pluripotent stem cells. These results reveal a pivotal role for an AS event in the regulation of pluripotency through the control of critical ESC-specific transcriptional programs.

引用

页码：132 / 146

页数：15

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