Analysis of Cell-cycle-specific Gene Expression in Human Cells As Determined by Microarrays and Double-thymidine Block Synchronization

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2002 Mar 21

PMID 11904377

Citations 32

Authors

Kerby Shedden

Stephen Cooper

Affiliations

Soon will be listed here.

Abstract

Microarray analysis of gene expression patterns for thousands of human genes has led to the proposal that a large number of genes are expressed in a cell-cycle-specific manner. The identification of cyclically expressed genes was based on Affymetrix microarray analysis of gene expression after double-thymidine block synchronization. A statistical reanalysis of the original data leads to three principal findings. (i) Randomized data exhibit periodic patterns of similar or greater strength than the experimental data. This finding suggests that all apparent cyclicities in the expression measurements may arise from chance fluctuations. (ii) The presence of cyclicity and the timing of peak cyclicity in a given gene are not reproduced in two replicate experiments. This fact suggests there is an uncontrolled source of experimental variation that is stronger than the innate variation of gene expression in cells over time. (iii) The amplitude of peak expression in the second cycle is not consistently smaller than the corresponding amplitude in the first cycle. This finding places doubt on the assumption that the cells are actually synchronized. We propose that the microarray results do not support the proposal that there are numerous cell-cycle-specifically expressed genes in human cells.

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References

Gong J, Traganos F, Darzynkiewicz Z . Growth imbalance and altered expression of cyclins B1, A, E, and D3 in MOLT-4 cells synchronized in the cell cycle by inhibitors of DNA replication. Cell Growth Differ. 1995; 6(11):1485-93. View

Cooper S . The continuum model: statistical implications. J Theor Biol. 1982; 94(4):783-800. DOI: 10.1016/0022-5193(82)90078-9. View

Cooper S . On the interpretation of the shortening of the G1-phase by overexpression of cyclins in mammalian cells. Exp Cell Res. 1998; 238(1):110-5. DOI: 10.1006/excr.1997.3807. View

Cho R, Huang M, Campbell M, Dong H, Steinmetz L, Sapinoso L . Transcriptional regulation and function during the human cell cycle. Nat Genet. 2001; 27(1):48-54. DOI: 10.1038/83751. View

Cooper S . Revisiting the relationship of the mammalian G1 phase to cell differentiation. J Theor Biol. 2001; 208(4):399-402. DOI: 10.1006/jtbi.2000.2228. View

Cooper S . A unifying model for the G1 period in prokaryotes and eukaryotes. Nature. 1979; 280(5717):17-9. DOI: 10.1038/280017a0. View

Cooper S . On the proposal of a G0 phase and the restriction point. FASEB J. 1998; 12(3):367-73. DOI: 10.1096/fasebj.12.3.367. View

Cooper S . The continuum model and G1-control of the mammalian cell cycle. Prog Cell Cycle Res. 2000; 4:27-39. DOI: 10.1007/978-1-4615-4253-7_3. View

Spellman P, Sherlock G, Zhang M, Iyer V, Anders K, Eisen M . Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol Biol Cell. 1998; 9(12):3273-97. PMC: 25624. DOI: 10.1091/mbc.9.12.3273. View

10.

Cho R, Campbell M, Winzeler E, Steinmetz L, Conway A, Wodicka L . A genome-wide transcriptional analysis of the mitotic cell cycle. Mol Cell. 1998; 2(1):65-73. DOI: 10.1016/s1097-2765(00)80114-8. View

11.

Cooper S . The continuum model and c-myc synthesis during the division cycle. J Theor Biol. 1988; 135(3):393-400. DOI: 10.1016/s0022-5193(88)80253-4. View

12.

Rao P, Johnson R . Mammalian cell fusion: studies on the regulation of DNA synthesis and mitosis. Nature. 1970; 225(5228):159-64. DOI: 10.1038/225159a0. View

13.

Cooper S, Shayman J . Revisiting retinoblastoma protein phosphorylation during the mammalian cell cycle. Cell Mol Life Sci. 2001; 58(4):580-95. PMC: 11146480. DOI: 10.1007/PL00000883. View

14.

Cooper S, Yu C, Shayman J . Phosphorylation-dephosphorylation of retinoblastoma protein not necessary for passage through the mammalian cell division cycle. IUBMB Life. 2000; 48(2):225-30. DOI: 10.1080/713803488. View

15.

Cooper S . Mammalian cells are not synchronized in G1-phase by starvation or inhibition: considerations of the fundamental concept of G1-phase synchronization. Cell Prolif. 1998; 31(1):9-16. PMC: 6496400. DOI: 10.1046/j.1365-2184.1998.00110.x. View

16.

Cooper S . On G0 and cell cycle controls. Bioessays. 1987; 7(5):220-3. DOI: 10.1002/bies.950070507. View