Gene profiling of cell cycle progression through S-phase reveals sequential expression of genes required for DNA replication and nucleosome assembly.
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.
van der Meijden
Caroline M J
CM
Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA..
Lapointe
David S
DS
Luong
Mai X
MX
Peric-Hupkes
Daniel
D
Cho
Brian
B
Stein
Janet L
JL
van Wijnen
Andre J
AJ
Stein
Gary S
GS
D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000235:genetics; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication / Q000235:genetics*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D016193:G1 Phase / Q000235:genetics; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006367:HeLa Cells; D006657:Histones / Q000235:genetics; D006801:Humans; D008938:Mitosis / Q000235:genetics; D009707:Nucleosomes / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000235:genetics / Q000378:metabolism; D016196:S Phase / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D006657:Histones; D009707:Nucleosomes; D014157:Transcription Factors; D012313:RNA; D004247:DNA