Delineation of a Human Histone H4 Cell Cycle Element in vivo: The Master Switch for H4 Gene Transcription

• Published in: Proceedings of the National Academy of Sciences - PNAS 1994-05, Vol.91 (10), p.4475-4479
• Main Authors: Ramsey-Ewing, Anna, Van Wijnen, Andre J., Stein, Gary S., Stein, Janet L.
• Format: Article
• Language: English
• Subjects: Base Composition; Base Sequence; binding; Binding Sites; Biochemistry; Cell cycle; Cell Cycle - physiology; Cell cycle proteins; Cell lines; Cell Nucleus - metabolism; Cellular biology; DNA; DNA, Neoplasm - metabolism; Gene Expression Regulation; Genes; Genetic mutation; Genetics; HeLa Cells; HiNF-M protein; histone H4; Histones; Histones - biosynthesis; Humans; Interphase; man; Molecular Sequence Data; Mutagenesis, Site-Directed; Nuclear Proteins - metabolism; Plasmids; Point Mutation; Promoter Regions, Genetic; promoters; Proteins; regulation; regulatory; Regulatory Sequences, Nucleic Acid; transcription; Transcription, Genetic; Transfection
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.10.4475

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.