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)-induc ible gene from P19 embryonal carcinoma cells that encodes a basic heli x-loop-helix (bHLH) protein that shows the highest sequence similariti es to the Drosophila Hairy and Enhancer of split and mouse Hes protein s. Stra13 does not bind to the known consensus motifs (E-box and N-box ) for bHLH proteins, but can repress activated transcription (through an or-helix rich domain) in part by interaction with general factors o f the basal transcription machinery. During mouse embryogenesis, Stra1 3 RNA is expressed in the neuroectoderm, and also in a number of mesod ermal 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/e ndodermal differentiation. This neuronal differentiation is accompanie d by an altered expression of mesodermal and neuronal markers, indicat ing that Stra13 could be one of the earliest RA target genes whose exp ression is required for repression of mesodermal/endodermal differenti ation and/or induction of neuronal differentiation when P19 cell aggre gates are exposed to RA. Our results raise the possibility that Stra13 could be involved as a repressor in a number of decision events occur ring during differentiation of various cell lineages.