title: A central role for TFIID in the pluripotent transcription circuitry.
abstract: 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.
authors.affiliation: Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
authors.forename: W W M Pim
authors.initials: WW
authors.lastname: Pijnappel
authors.forename: Daniel
authors.initials: D
authors.lastname: Esch
authors.forename: Marijke P A
authors.initials: MP
authors.lastname: Baltissen
authors.forename: Guangming
authors.initials: G
authors.lastname: Wu
authors.forename: Nikolai
authors.initials: N
authors.lastname: Mischerikow
authors.forename: Atze J
authors.initials: AJ
authors.lastname: Bergsma
authors.forename: Erik
authors.initials: E
authors.lastname: van der Wal
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Han
authors.forename: Hermann vom
authors.initials: Hv
authors.lastname: Bruch
authors.forename: Sören
authors.initials: S
authors.lastname: Moritz
authors.forename: Phillip
authors.initials: P
authors.lastname: Lijnzaad
authors.forename: A F Maarten
authors.initials: AF
authors.lastname: Altelaar
authors.forename: Katrin
authors.initials: K
authors.lastname: Sameith
authors.forename: Holm
authors.initials: H
authors.lastname: Zaehres
authors.forename: Albert J R
authors.initials: AJ
authors.lastname: Heck
authors.forename: Frank C P
authors.initials: FC
authors.lastname: Holstege
authors.forename: Hans R
authors.initials: HR
authors.lastname: Schöler
authors.forename: H T Marc
authors.initials: HT
authors.lastname: Timmers
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming / Q000235:genetics; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D008297:Male; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012319:RNA Polymerase II / Q000378:metabolism; D035381:TATA-Binding Protein Associated Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D035181:TATA-Box Binding Protein / Q000378:metabolism; D035362:Transcription Factor TFIID / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D012319:RNA Polymerase II