DERMO-1 - A NOVEL TWIST-RELATED BHLH PROTEIN EXPRESSED IN THE DEVELOPING DERMIS

Transcription factors belonging to the basic helix-loop-helix (bHLH) f amily have been shown to control differentiation of a variety of cell types. Tissue-specific bHLH proteins dimerize preferentially with ubiq uitous bHLH proteins to form heterodimers that bind the E-box consensu s sequence (CANNTG) in the control regions of target genes. Using the yeast two-hybrid system to screen for tissue-specific bHLH proteins, w hich dimerize with the ubiquitous bHLH protein E12, we cloned a novel bHLH protein, named Dermo-l. Within its bHLH region, Dermo-l shares ex tensive homology with members of the twist family of bHLH proteins, wh ich are expressed in embryonic mesoderm. During mouse embryogenesis, D ermo-1 showed an expression pattern similar to, but distinct from, tha t of mouse twist. Dermo-l was expressed at a low level in the scleroto me and dermatome of the somites, and in the limb buds at Day 10.5 post coitum (p.c.), and accumulated predominantly in the dermatome, prever tebrae, and the derivatives of the branchial arches by Day 13.5 p.c. A s differentiation of prechondrial cells proceeded, Dermo-l expression became restricted to the perichondrium. Expression of Dermo-l increase d continuously in the dermis through Day 17.5 p.c. and was also detect ed in the dermis of neonates, but became downregulated in adult tissue s. The Dermo-l protein bound the E-box consensus sequence in the prese nce of E12, but transcriptional activity was not detectable. Instead, Dermo-l repressed transcriptional activity of myogenic bHLH proteins. The expression pattern of Dermo-l suggests that it functions as a regu lator of gene expression in a subset of mesenchymal cell lineages incl uding developing dermis. (C) 1995 Academic Press, Inc.