An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming

Mathieu Gabut, Payman Samavarchi-Tehrani, Xinchen Wang, Valentina Slobodeniuc, Dave O'Hanlon, Hoon-Ki Sung, Manuel Alvarez, Shaheynoor Talukder, Qun Pan, Esteban O Mazzoni, Stephane Nedelec, Hynek Wichterle, Knut Woltjen, Timothy R Hughes, Peter W Zandstra, Andras Nagy, Jeffrey L Wrana, Benjamin J Blencowe
Cell 2011 September 30, 147 (1): 132-46
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.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"