title: Genes involved in cell adhesion and signaling: a new repertoire of retinoic acid receptor target genes in mouse embryonic fibroblasts.
abstract: Nuclear retinoic acid (RA) receptors (RARα, β and γ) are ligand-dependent transcription factors that regulate the expression of a battery of genes involved in cell differentiation and proliferation. They are also phosphoproteins and we previously showed the importance of their phosphorylation in their transcriptional activity. In the study reported here, we conducted a genome-wide analysis of the genes that are regulated by RARs in mouse embryonic fibroblasts (MEFs) by comparing wild-type MEFs to MEFs lacking the three RARs. We found that in the absence of RA, RARs control the expression of several gene transcripts associated with cell adhesion. Consequently the knockout MEFs are unable to adhere and to spread on substrates and they display a disrupted network of actin filaments, compared with the WT cells. In contrast, in the presence of the ligand, RARs control the expression of other genes involved in signaling and in RA metabolism. Taking advantage of rescue cell lines expressing the RARα or RARγ subtypes (either wild-type or mutated at the N-terminal phosphorylation sites) in the null background, we found that the expression of RA-target genes can be controlled either by a specific single RAR or by a combination of RAR isotypes, depending on the gene. We also selected genes that require the phosphorylation of the receptors for their regulation by RA. Our results increase the repertoire of genes that are regulated by RARs and highlight the complexity and diversity of the transcriptional programs regulated by RARs, depending on the gene.
authors.affiliation: IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), INSERM, U964, CNRS, UMR7104, Université de Strasbourg, 1 rue Laurent Fries, BP 10142, 67404 Illkirch Cedex, France.
authors.forename: Ziad
authors.initials: Z
authors.lastname: Al Tanoury
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Piskunov
authors.forename: Dina
authors.initials: D
authors.lastname: Andriamoratsiresy
authors.forename: Samia
authors.initials: S
authors.lastname: Gaouar
authors.forename: Régis
authors.initials: R
authors.lastname: Lutzing
authors.forename: Tao
authors.initials: T
authors.lastname: Ye
authors.forename: Bernard
authors.initials: B
authors.lastname: Jost
authors.forename: Céline
authors.initials: C
authors.lastname: Keime
authors.forename: Cécile
authors.initials: C
authors.lastname: Rochette-Egly
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D010766:Phosphorylation; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis* / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D015398:Signal Transduction; D000097768:Retinoic Acid Receptor gamma
chemical_list: D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D000097768:Retinoic Acid Receptor gamma; C000607072:Rara protein, mouse; C082925:retinoic acid receptor beta
keywords: Adhesion; Nuclear receptors; Retinoic acid; Transcription