1. Gene profiling of cell cycle progression through S-phase reveals sequential expression of genes required for DNA replication and nucleosome assembly.
- Author
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van der Meijden CM, Lapointe DS, Luong MX, Peric-Hupkes D, Cho B, Stein JL, van Wijnen AJ, and Stein GS
- Subjects
- Cell Division genetics, DNA biosynthesis, DNA genetics, DNA Repair genetics, E2F Transcription Factors, G1 Phase genetics, Gene Expression Profiling, HeLa Cells, Histones genetics, Humans, Mitosis genetics, Nucleosomes metabolism, Oligonucleotide Array Sequence Analysis, RNA genetics, RNA metabolism, S Phase genetics, Transcription Factors genetics, Cell Cycle genetics, Cell Cycle Proteins, DNA Replication genetics, DNA-Binding Proteins, Gene Expression Regulation, Leukemic, Nucleosomes genetics
- Abstract
The ordered expression of genes after growth factor stimulation in G(1) supportsthe onset of DNA replication. To characterize regulatory events during S-phase when cell cycle progression has become growth factor independent, we have profiled the expression of over 7,000 human genes using GeneChip DNA microarray analysis. HeLa cells were synchronized at the beginning of S-phase by thymidine/aphidicolin block, and RNA populations were analyzed throughout the S and G(2) phases. Expression of genes involved in DNA replication is maximal during early S-phase, whereas histone mRNAs peak at mid S-phase. Genes related to cell proliferation, including those encoding cyclins, oncoproteins, growth factors, proteins involved in signal transduction, and DNA repair proteins, follow distinct temporal patterns of expression that are functionally linked to initiation of DNA replication and progression through S-phase. The timing of expression for many genes in tumor-derived HeLa cells is highly conserved when compared with normal cells. In contrast, a number of genes show growth phenotype-related expression patterns that may directly reflect loss of stringent growth control in tumor cells. Our data reveal there is a core subset of cell growth-related genes that is fundamental to cycling cells irrespective of cell growth phenotype.
- Published
- 2002