Cooperation between C/EBPα TBP/TFIIB and SWI/SNF recruiting domains is required for adipocyte differentiation (original) (raw)
- Thomas Åskov Pedersen1,3,
- Elisabeth Kowenz-Leutz2,3,
- Achim Leutz2,4, and
- Claus Nerlov1,4
- 1Laboratory of Gene Therapy Research, Copenhagen University Hospital, 2100 Copenhagen, Denmark; 2Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany
Abstract
Chromatin remodeling is an important step in promoter activation during cellular lineage commitment and differentiation. We show that the ability of the C/EBPα transcription factor to direct adipocyte differentiation of uncommitted fibroblast precursors and to activate SWI/SNF-dependent myeloid-specific genes depends on a domain, C/EBPα transactivation element III (TE-III), that binds the SWI/SNF chromatin remodeling complex. TE-III collaborates with C/EBPα TBP/TFIIB interaction motifs during induction of adipogenesis and adipocyte-specific gene expression. These results indicate that C/EBPα acts as a lineage-instructive transcription factor through SWI/SNF-dependent modification of the chromatin structure of lineage-specific genes, followed by direct promoter activation via recruitment of the basal transcription–initiation complex, and provide a mechanism by which C/EBPα can mediate differentiation along multiple cellular lineages.
Footnotes
↵3 These authors contributed equally to this work.
↵4 Corresponding authors.
E-MAIL aleutz{at}mdc-berlin.de; FAX 49-30-9406-3298.
E-MAIL nerlov{at}embl-monterotundo.it; FAX 39-06-9009-1272.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.209901.
- Received June 11, 2001.
- Accepted September 28, 2001.
Cold Spring Harbor Laboratory Press