Competence growth factors can cause modification in higher-order chromatin structure in mouse embryo 3T3 fibroblasts

The authors compared sedimentation rates of nucleoids from mouse embryo 3T3 fibroblasts cultured in the presence or absence of different cell growth factors. The results clearly showed that rapidly sedimenting nucleoids are obtained only when cells are supplied with any of the following competence growth factors: platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), or the product of the oncogene v-sis (a peptide homologous to PDGF). The tumor promoter phorbol 12-myristate 13-acetate, an activator of protein kinase C and a partial mitogen, shares this property with the competence growth factors. Removal of these factors from the medium causes cells to enter Go and nucleoids to sediment at a slower rate. Protein synthesis is required for growth factor induction of change in nucleoid sedimentation, but inhibition of either DNA synthesis or DNA repair does not antagonize the effect of growth factors. Titration of nucleoids with ethidium bromide indicates that one possible mechanism for the nucleoid change is the unwinding of DNA in supercoiled loops. The results indicated that the nucleoid change constitutes a cell response to competence factors that might have an important role in cell proliferation.