[en] All-trans retinoic acid (RA) induces transforming growth factor beta (TGF-beta)-dependent autocrine growth of mouse embryonic fibroblasts (MEFs). We have used chromatin immunoprecipitation to map 354 RA receptor (RAR) binding loci in MEFs, most of which were similarly occupied by the RAR alpha and RAR gamma receptors. Only a subset of the genes associated with these loci are regulated by RA, among which are several critical components of the TGF-beta pathway. We also show RAR binding to a novel series of target genes involved in cell cycle regulation, transformation, and metastasis, suggesting new pathways by which RA may regulate proliferation and cancer. Few of the RAR binding loci contained consensus direct-repeat (DR)-type elements. The majority comprised either degenerate DRs or no identifiable DRs but anomalously spaced half sites. Furthermore, we identify 462 RAR target loci in embryonic stem (ES) cells and show that their occupancy is cell type specific. Our results also show that differences in the chromatin landscape regulate the accessibility of a subset of more than 700 identified loci to RARs, thus modulating the repertoire of target genes that can be regulated and the biological effects of RA.
Research center :
Giga-Neurosciences - ULiège IGBMC
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Delacroix, Laurence ; Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Moutier, Emmanuel
Altobelli, Gioia
Legras, Stephanie
Poch, Olivier
Choukrallah, Mohamed-Amin
Bertin, Isabelle
Jost, Bernard
Davidson, Irwin
Language :
English
Title :
Cell-specific interaction of retinoic acid receptors with target genes in mouse embryonic fibroblasts and embryonic stem cells.
Publication date :
2010
Journal title :
Molecular and Cellular Biology
ISSN :
0270-7306
eISSN :
1098-5549
Publisher :
American Society for Microbiology (ASM), Washington, United States - District of Columbia
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