Gene activation in human diploid cells: Age-dependent modifications in the stability of messenger RNAs for nonhistone chromosomal proteins

Abstract

Serum stimulation of early as well as late passages of nondividing WI-38 human diploid fibroblasts to proliferate, results in DNA synthesis beginning at 12 hours and mitosis at 20 hours. A 2-fold increase in the transcriptional activity of chromatin isolated from early and late passage WI-38 cells is evident one hour following serum stimulation. An increased synthesis and association with the genome of two defined molecular weight classes of nonhistone chromosomal proteins one hour following serum stimulation of early and late passage cells is also observed. The increased chromatin template activity and nonhistone chromosomal protein synthesis occur in early passage cells stimulated to proliferate in the presence of actinomycin D. However, when late passage WI-38 cells are stimulated in the presence of actinomycin D, increases in chromatin template activity and nonhistone chromosomal protein synthesis are not observed one hour following serum stimulation. The possibility that nonhistone chromosomal protein synthesis and activation of transcription early during the prereplicative phase of the cell cycle in early passage human diploid fibroblasts may be regulated at the translational level is discussed. Consideration is also given to the possibility that there may be an age-dependent modification in such a regulatory mechanism.