Transcription of human histone genes in extracts from synchronized HeLa cells

Nuclear extracts were prepared from synchronized HeLa cells at various times during the cell cycle and assayed for the ability to transcribe several cellular and viral genes. The efficiency of transcription of a human histone H4 gene is 3- to 10-fold greater in nuclear extracts from S phase nuclei than in extracts from non-S phase cells. In contrast, the adenovirus virus type 2 (Ad2) major late promoter is utilized 3- to 20-fold more efficiently in nuclear extracts from non-S phase cells. Transcription of other genes, including a human histone H3 and the simian virus 40 late transcription unit, is equally efficient in S and non-S phase extracts. Mixing experiments demonstrate that the rate-limiting activities for histone H4 and Ad2 major late transcription function independently and that the effects of these activities are additive. Competition studies suggest that the H4-specific transcription activity can be sequestered by preincubation with the H4 template DNA. These data support the concept that cell cycle regulation of human histone gene transcription may depend in part on soluble transcription activities that are modulated during the cell cycle. Further, in addition to the H4-specific transcription activity, there may exist other transcription factors whose activity can fluctuate according to the cell cycle or according to the growth state of the cells.