ALTERED EXPRESSION OF THE TWIST GENE IN YOUNG VERSUS SENESCENT HUMAN-DIPLOID FIBROBLASTS

We have recently reported the cloning and characterization of the huma n twist gene (W-twist), which encodes an evolutionarily conserved heli x-loop-helix transcription factor. In several species, twist has been shown to play a role in mesoderm differentiation. We now report on the differential expression of H-twist as a function of in vitro life spa n in human diploid fibroblasts. Ii-twist was found to be expressed at a relatively high level in quiescent young cells. Addition of fresh se rum to young G(0) cultures results in a rapid repression of H-twist mR NA expression. This repression depends on the presence of growth facto rs, specifically EGF, and requires protein synthesis. mRNA stability s tudies using either actinomycin D or alpha-amanitin indicate a similar decay rate of HP-twist mRNA in both young and senescent cells, sugges ting that the differential expression of H-twist in young versus old i s not primarily regulated at the level of mRNA turnover. (C) 1996 Acad emic Press, Inc.