Transcriptional activation of beta-tropomyosin mediated by serum response factor and a novel barx homologue, Barx1b, in smooth muscle cells

Tropomyosin (TM) is a regulatory protein of actomyosin system. Muscle type- specific expression of TM isoforms is generated from different genes and by alternative splicing. beta -TM isoforms in chicken skeletal and smooth mus cles are encoded by a single gene and transcribed from the same promoter. W e previously reported a smooth muscle cell (SMC) phenotype-dependent change in beta -TM expression (Kashiwada, K., Nishida, W,, Hayashi, K,, Ozawa, K. , Yamanaka, Y,, Saga, H,, Yamashita, T,, Tohyama, M,, Shimada, S,, Sate, K, , and Sobue, K, (1997) J. Biol. Chem. 272, 15396-15404), and identified bet a -TM as an SMC-differentiation marker. Here, we characterized the transcri ptional machinery of the beta -TM gene in SMCs. Promoter and gel mobility s hift analyses revealed an obligatory role for serum response factor and its interaction with the CArG box sequence in the SMC-specific transcription o f the beta -TM gene in differentiated SMCs, We further isolated a novel hom ologue of the Barx homeoprotein family, Barx1b, from chicken gizzard, Barx1 b was exclusively localized to SMCs of the upper digestive organs and their attached arteries and to craniofacial structures. Serum response factor an d Barx1b bound each other directly, coordinately transactivated the beta -T M gene in differentiated SMCs and heterologous cells, and formed a ternary complex with a CArG probe. Taken together, these results suggest that SRF a nd Barx1b are coordinately involved in the SMC-specific transcription of th e beta -TM gene in the upper digestive organs and their attached arteries.