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Transcriptional regulation and function during the human cell cycle

Nature Genetics volume 27, pages 48–54 (2001)Cite this article

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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Author notes

  1. Raymond J. Cho

    Present address: InGenuity Systems, Inc., Alviso, California, USA

  2. Michael J. Campbell

    Present address: Celera Genomics, Foster City, California, USA

  3. Raymond J. Cho, Mingxia Huang and Michael J. Campbell: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Genetics, Stanford University School of Medicine, Stanford, California, USA

    Raymond J. Cho, Lars Steinmetz & Ronald W. Davis

  2. Department of Biochemistry and Molecular Biology, Department of Molecular and Human Genetics, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, USA

    Mingxia Huang & Stephen J. Elledge

  3. Molecular Applications Group, Palo Alto, California, USA

    Michael J. Campbell

  4. Affymetrix, Inc., Santa Clara, California, USA

    Helin Dong & David J. Lockhart

  5. Department of Biochemistry, Stanford University School of Medicine, Stanford, California, USA

    Ronald W. Davis

  6. Genomics Institute of the Novartis Research Foundation, San Diego, California, USA

    Lisa Sapinoso & Garret Hampton

  7. Salk Institute for Biological Studies, Laboratory of Genetics, La Jolla, California, USA

    David J. Lockhart

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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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