A central role for TFIID in the pluripotent transcription circuitry

W. W.M.Pim Pijnappel, Daniel Esch, Marijke P.A. Baltissen, Guangming Wu, Nikolai Mischerikow, Atze J. Bergsma, Erik Van Der Wal, Dong Wook Han, Hermann Vom Bruch, Sören Moritz, Phillip Lijnzaad, A. F.Maarten Altelaar, Katrin Sameith, Holm Zaehres, Albert J.R. Heck, Frank C.P. Holstege, Hans R. Schöler, H. T.Marc Timmers

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

65 Citaten (Scopus)

Samenvatting

Embryonic stem (ES) cells are pluripotent and characterized by open chromatin and high transcription levels, achieved through auto-regulatory and feed-forward transcription factor loops. ES-cell identity is maintained by a core of factors including Oct4 (also known as Pou5f1), Sox2, Klf4, c-Myc (OSKM) and Nanog, and forced expression of the OSKM factors can reprogram somatic cells into induced pluripotent stem cells (iPSCs) resembling ES cells. These gene-specific factors for RNA-polymerase-II-mediated transcription recruit transcriptional cofactors and chromatin regulators that control access to and activity of the basal transcription machinery on gene promoters. How the basal transcription machinery is involved in setting and maintaining the pluripotent state is unclear. Here we show that knockdown of the transcription factor IID (TFIID) complex affects the pluripotent circuitry in mouse ES cells and inhibits reprogramming of fibroblasts. TFIID subunits and the OSKM factors form a feed-forward loop to induce and maintain a stable transcription state. Notably, transient expression of TFIID subunits greatly enhanced reprogramming. These results show that TFIID is critical for transcription-factor-mediated reprogramming. We anticipate that, by creating plasticity in gene expression programs, transcription complexes such as TFIID assist reprogramming into different cellular states.

Originele taal-2Engels
Pagina's (van-tot)516-519
Aantal pagina's4
TijdschriftNature
Volume495
Nummer van het tijdschrift7442
DOI's
StatusGepubliceerd - 28 mrt. 2013
Extern gepubliceerdJa

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