Open AccessCell-Specific Interaction of Retinoic Acid Receptors with Target Genes in Mouse Embryonic Fibroblasts and Embryonic Stem Cells
Author(s) -
Laurence Delacroix,
Emmanuel Moutier,
Gioia Altobelli,
Stéphanie Legras,
Olivier Poch,
Mohamed-Amin Choukrallah,
Isabelle Bertin,
Bernard Jost,
Irwin Davidson
Publication year - 2010
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00756-09
Subject(s) - biology , embryonic stem cell , retinoic acid , microbiology and biotechnology , chromatin immunoprecipitation , autocrine signalling , chromatin , receptor , gene , genetics , promoter , gene expression
All-trans retinoic acid (RA) induces transforming growth factor beta (TGF-β)-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 RARα and RARγ receptors. Only a subset of the genes associated with these loci are regulated by RA, among which are several critical components of the TGF-β 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.