Reexpression of retinoic acid receptor (RAR) gamma or overexpression of RAR alpha or RAR beta in RAR gamma-null F9 cells reveals a partial functional redundancy between the three RAR types.
Disruption of retinoic acid receptor (RAR) gamma in F9 embryonal carcinoma cells leads to aberrent differentiation and reduced activation of expression of several all-trans-retinoic acid (RA)-induced genes. We have analyzed the expression of several additional RA-responsive genes in RAR alpha- and RAR gamma-null F9 cells. The RA-induced activation of Cdx1, Gap43, Stra4, and Stra6 was specifically impaired in RAR gamma-null cells, supporting the idea that each RAR may regulate distinct subsets of target genes. To further investigate the role of RAR gamma in F9 cell differentiation, "rescue" cell lines reexpressing RAR gamma 2 or overexpressing either RAR alpha 1 or RAR beta 2 were established in RAR gamma-null cells. Reexpression of RAR gamma or overexpression of RAR alpha restored both target-gene activation and the differentiation potential. In contrast, over-expression of RAR beta only poorly restored differentiation, although it could replace RAR gamma for the activation of target genes. Functional redundancy between the various RARs is discussed.
Taneja
R
R
Institut de Génétique et de Biologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Medicale/Université Louis Pasteur, Collège de France, Illkirch.
Bouillet
P
P
Boylan
J F
JF
Gaub
M P
MP
Roy
B
B
Gudas
L J
LJ
Chambon
P
P
D000818:Animals; D000911:Antibodies, Monoclonal; D030161:Avian Proteins; D015152:Blotting, Northern; D018236:Carcinoma, Embryonal; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D019922:GAP-43 Protein; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D010750:Phosphoproteins / Q000096:biosynthesis; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis*; D000072482:Retinoic Acid Receptor alpha; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000097768:Retinoic Acid Receptor gamma
D000911:Antibodies, Monoclonal; D030161:Avian Proteins; D004268:DNA-Binding Proteins; D019922:GAP-43 Protein; D018398:Homeodomain Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; D000097768:Retinoic Acid Receptor gamma; C491272:Cdx1 protein, mouse; C000607072:Rara protein, mouse; C082925:retinoic acid receptor beta