DIFFERENTIATION-DEPENDENT EXPRESSION IN MUSCLE-CELLS OF ZT3, A NOVEL ZINC-FINGER FACTOR DIFFERENTIALLY EXPRESSED IN EMBRYONIC AND ADULT TISSUES

ZT3, isolated from a murine muscle cell cDNA library by a low-stringen cy hybridization, encodes a zinc finger domain containing factor with a transcript of 5.0 kb. A 3' 2.5 kb partial nucleotide sequence contai ns an ORF of 1.5 kb where 17 canonical C2H2 zinc finger domains organi zed in tandem were identified, It maps on mouse chromosome 11, close t o two mutations which affect skeletal formation. ZT3 expression depend s upon differentiation of myogenic cells in culture, since it is upreg ulated with myogenin and inhibited in scr-transfected C2Cl2 cells. ZT3 is not expressed in NIH3T3 or C3H10T1/2 fibroblasts, but is induced w hen fibroblasts are myogenically converted by transfection with the mu scle regulatory genes (MRFs). Its expression is also upregulated in th e rhabdomyosarcoma cell line RD induced to myogenic differentiation by TPA treatment. In postimplantation embryos, ZT3 is diffusely expresse d but higher expression is detectable in the neural tube and encephali c vesicles, in the somites and, at a high level, in the limb buds as t hey form. During further development ZT3 is expressed in many tissues of neuroectodermal and mesodermal origin, but its expression decreases during fetal development and in the adult it is restricted to skeleta l and cardiac muscle and to spleen. This pattern of expression suggest s a possible role played by ZT3 in differentiating skeletal muscle. It s expression in other tissues is compatible with the suggestion that m embers of this class of DNA-binding factors play different roles durin g post-implantation development and in the adult life.