Non-histone chromosomal proteins: their role in the regulation of histone-gene expression

Histone-gene expression was studied during the cell cycle of continuously dividing HeLa S3 cells and after stimulation of confluent monolayers of WI-38 human diploid fibroblasts to proliferate. The presence of histone-mRNA sequences was assayed by hybridization to a 3H-labelled single-stranded DNA complementary to histone-mRNA molecules. In HeLa S3 cells histone mRNA sequences were found in the nucleus and associated with polyribosomes during S-phase, but not during G1-phase. Transcripts of S-phase chromatin contained histone-mRNA sequences, but those of G1-phase chromatin did not. Similarly, in WI-38 cells association of histone-mRNA sequences with polyribosomes and transcription of histone-mRNA sequences from chromatin parallel DNA replication. Taken together these results suggest that the regulation of histone-gene expression resides, at least in part, at the transcriptional level. Chromatin-reconstitution studies provide evidence that non-histone chromosomal proteins play a key role in activation of histone-gene transcription during the period of the cell cycle when DNA is replicated. Phosphate groups associated with the S-phase non-histone chromosomal proteins appear to be functionally involved in the control of histone-gene readout.