Coordinate regulation of multiple histone mRNAs during the cell cycle in HeLa cells

Core histone gene expression in HeLa S3 cells has been examined as a function of the cell cycle using cloned human histone gene probes. Total cellular histone mRNAs were analyzed by Northern blot analysis, and their relative abundance shown to be temporally coupled to DNA synthesis rates in S phase. The in vivo incorporation of 3H-uridine into at least fifteen heterologous histone mRNAs (in one hour pulse intervals at various times in the cell cycle), was monitored by hybrid selection. Hybridized RNAs were eluted and resolved electrophoretically to give both a quantitative and qualitative assay for multiple mRNA species. Maximal incorporation of 3H-uridine into histone mRNAs precedes their maximal accumulation, indicating that transcriptional regulation is predominant in early S phase. The turnover of histone mRNAs in late S occurs in the presence of a reduced apparent transcription rate, indicating that post-transcriptional regulation is predominant in late S. All the detected multiple histone mRNAs are coordinately regulated during the HeLa cell cycle.