Chromatin as a model system for studying the regulation of histone gene expression in mammalian cells : (mRNA, chromosomal proteins, transcription, cell cycle)

Abstract

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-tabeted, 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. However, other results suggest that the coupling of histone gene expression and DNA synthesis is mediated post-transcriptionally. Chromatin reconstitution studies provide evidence that (i) a component of the complex and heterogeneous non histone chromosomal proteins plays a key role in activation or derepression of histone gene transcription during the period of the cell cycle when DNA is replicated, (ii) the chromosomal proteins and/or the DNA sequences involved in the regulation of histone gene expression may be similar in mouse and human and (iii) phosphate groups associated with the S phase non histone chromosomal proteins appear to be functionally involved in the control of histone gene readout.