Transcriptional regulation and function during the human cell cycle

Abstract

We report here the transcriptional profiling of the cell cycle on a genome-wide scale in human fibroblasts. We identified approximately 700 genes that display transcriptional fluctuation with a periodicity consistent with that of the cell cycle. Systematic analysis of these genes revealed functional organization within groups of coregulated transcripts. A diverse set of cytoskeletal reorganization genes exhibit cell-cycle–dependent regulation, indicating that biological pathways are redirected for the execution of cell division. Many genes involved in cell motility and remodeling of the extracellular matrix are expressed predominantly in M phase, indicating a mechanism for balancing proliferative and invasive cellular behavior. Transcripts upregulated during S phase displayed extensive overlap with genes induced by DNA damage; cell-cycle–regulated transcripts may therefore constitute coherent programs used in response to external stimuli. Our data also provide clues to biological function for hundreds of previously uncharacterized human genes.

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Figure 1: Clustering analysis of cell-cycle–regulated transcripts.
Figure 2: Over- and under-representation of genes in biological functional categories in cell-cycle–regulated expression clusters, as calculated by the binomial distribution function.
Figure 3: Cell-cycle regulation of human genes with related biological function.

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Acknowledgements

We thank D. Galloway for providing the cell line; L. Wodicka for help with experiments; M. Ho for help with data analysis; M. Mittmann and D. Balaban for array design; Affymetrix Product Development for array testing and validation; F.F. Cai for help in construction of the human functional database; and M. Mindrinos, S. Chang, C. Chon, J. Yang and N. Thayer for discussions and a critical reading of the manuscript. This work was supported in part by NIH grants to S.J.E. and R.W.D.

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Correspondence to Michael J. Campbell.

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Cho, R., Huang, M., Campbell, M. et al. Transcriptional regulation and function during the human cell cycle. Nat Genet 27, 48–54 (2001). https://doi.org/10.1038/83751

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