GSBS Student Publications

Title

Coordinate control and selective expression of the full complement of replication-dependent histone H4 genes in normal and cancer cells

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cell Biology and Cancer Center

Date

9-1-2005

Document Type

Article

Medical Subject Headings

Animals; Base Sequence; Cell Line; Consensus Sequence; DNA Replication; Gene Expression Profiling; *Gene Expression Regulation; *Gene Expression Regulation, Neoplastic; Histones; Humans; Promoter Regions (Genetics); RNA, Messenger; S Phase; Signal Transduction

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The replication of eukaryotic genomes necessitates the coordination of histone biosynthesis with DNA replication at the onset of S phase. The multiple histone H4 genes encode identical proteins, but their regulatory sequences differ. The contributions of these individual genes to histone H4 mRNA expression have not been described. We have determined, by real-time quantitative PCR and RNase protection, that the human histone H4 genes are not equally expressed and that a subset contributes disproportionately to the total pool of H4 mRNA. Differences in histone H4 gene expression can be attributed to observed unequal activities of the H4 gene promoters, which exhibit variations in gene regulatory elements. The overall expression pattern of the histone H4 gene complement is similar in normal and cancer cells. However, H4 genes that are moderately expressed in normal cells are sporadically silenced in tumor cells with compensation of expression by other H4 gene copies. Chromatin immunoprecipitation analyses and in vitro DNA binding assays indicated that 11 of the 15 histone H4 genes interact with the cell cycle regulatory histone nuclear factor P, which forms a complex with the cyclin E/CDK2-responsive co-regulator p220(NPAT). These 11 H4 genes account for 95% of the histone H4 mRNA pool. We conclude that the cyclin E/CDK2/p220(NPAT)/histone nuclear factor P signaling pathway is the principal regulator of histone H4 biosynthesis.

Rights and Permissions

Citation: J Biol Chem. 2005 Nov 11;280(45):37400-7. Epub 2005 Aug 29. Link to article on publisher's site

Related Resources

Link to article in PubMed

Journal Title

The Journal of biological chemistry

PubMed ID

16131487