Delineation of a human histone H4 cell cycle element in vivo: the master switch for H4 gene transcription
Graduate School of Biomedical Sciences; Graduate School of Biomedical Sciences; Department of Cell Biology
Medical Subject Headings
Base Composition; Base Sequence; Binding Sites; Cell Cycle; Cell Nucleus; DNA, Neoplasm; *Gene Expression Regulation; Hela Cells; Histones; Humans; Molecular Sequence Data; Mutagenesis, Site-Directed; Nuclear Proteins; Point Mutation; *Promoter Regions (Genetics); Regulatory Sequences, Nucleic Acid; *Transcription, Genetic; Transfection
Life Sciences | Medicine and Health Sciences
Histone gene expression is cell cycle regulated at the transcriptional and the post-transcriptional levels. Upon entry into S phase, histone gene transcription is stimulated 2- to 5-fold and peaks within 1-3 hr of the initiation of DNA synthesis. We have delineated the proximal promoter element responsible for cell cycle-dependent transcription of a human histone H4 gene in vivo. Our results indicate that H4 cell cycle-dependent transcriptional regulation is mediated by an 11-base-pair element, the cell cycle element (5'-CTTTCG-GTTTT-3'), that resides in the in vivo protein-DNA interaction site, site II (nucleotides -64 to -24). The H4 cell cycle element functions as a master switch for expression of the FO108 human histone H4 gene in vivo; mutations within the H4 cell cycle element drastically reduce the level of expression as well as abrogate cell cycle-regulated transcription. Furthermore, these mutations result in a loss of binding in vitro of the cognate nuclear factor HiNF-M. In vivo competition analysis indicates that the cell cycle element mediates specific competition for a DNA-binding factor, presumably HiNF-M, that is a rate-limiting step in transcription of this H4 gene.
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Citation: Proc Natl Acad Sci U S A. 1994 May 10;91(10):4475-9.
Proceedings of the National Academy of Sciences of the United States of America
Ramsey-Ewing, Anna L.; Van Wijnen, Andre J.; Stein, Gary S.; and Stein, Janet L., "Delineation of a human histone H4 cell cycle element in vivo: the master switch for H4 gene transcription" (1994). GSBS Student Publications. 1011.