Phenotype suppression: a postulated molecular mechanism for mediating the relationship of proliferation and differentiation by Fos/Jun interactions at AP-1 sites in steroid responsive promoter elements of tissue-specific genes.

There is a generalized reciprocal relationship between cell growth and expression of genes that occurs following completion of proliferation, which supports the progressive development of cell and tissue phenotypes. Molecular mechanisms which couple the shutdown of proliferation with initiation of tissue-specific gene transcription have been addressed experimentally in cultures of primary diploid osteoblasts that undergo a growth and differentiation developmental sequence. Evidence is presented for a model which postulates that genes transcribed post-proliferatively are suppressed during cell growth by binding of the Fos/Jun protein complex to AP-1 promoter sites associated with vitamin D responsive elements of several genes encoding osteoblast phenotype markers (Type I collagen, alkaline phosphatase, osteocalcin).