Overexpression of Stra13, a novel retinoic acid-inducible gene of the basic helix-loop-helix family, inhibits mesodermal and promotes neuronal differentiation of P19 cells.
We report the cDNA cloning of Stra13, a novel retinoic acid (RA)-inducible gene from P19 embryonal carcinoma cells that encodes a basic helix-loop-helix (bHLH) protein that shows the highest sequence similarities to the Drosophila Hairy and Enhancer of split and mouse Hes proteins. Stra13 does not bind to the known consensus motifs (E-box and N-box) for bHLH proteins, but can repress activated transcription (through an alpha-helix rich domain) in part by interaction with general factors of the basal transcription machinery. During mouse embryogenesis, Stra13 RNA is expressed in the neuroectoderm, and also in a number of mesodermal and endodermal derivatives. Remarkably, overexpression of Stra13 in P19 cells results in neuronal differentiation in monolayer culture, under conditions where wild-type P19 cells only undergo mesodermal/endodermal differentiation. This neuronal differentiation is accompanied by an altered expression of mesodermal and neuronal markers, indicating that Stra13 could be one of the earliest RA target genes whose expression is required for repression of mesodermal/endodermal differentiation and/or induction of neuronal differentiation when P19 cell aggregates are exposed to RA. Our results raise the possibility that Stra13 could be involved as a repressor in a number of decision events occurring during differentiation of various cell lineages.
Boudjelal
M
M
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique-Institut National de la Santé et de la Recherche Médicale-Université Louis Pasteur, Collège de France, Illkirch.
Taneja
R
R
Matsubara
S
S
Bouillet
P
P
Dolle
P
P
Chambon
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D019556:COS Cells; D002277:Carcinoma / Q000188:drug therapy / Q000196:embryology / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008648:Mesoderm / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects*; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; D014212:Tretinoin; C499317:Ascl1 protein, mouse; C491539:Bhlhe40 protein, mouse