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Marking of active genes on mitotic chromosomes

Nature volume 388, pages 895–899 (1997)Cite this article

Abstract

During development and differentiation, cellular phenotypes are stably propagated through numerous cell divisions1. This epigenetic ‘cell memory’ helps to maintain stable patterns of gene expression2. DNA methylation3 and the propagation of specific chromatin structures may both contribute to cell memory4. There are two impediments during the cell cycle that can hinder the inheritance of specific chromatin configurations: first, the pertinent structures must endure the passage of DNA-replication forks in S phase5; second, the chromatin state must survive mitosis, when chromatin condenses, transcription is turned off, and almost all double-stranded DNA-binding proteins are displaced6,7. After mitosis, the previous pattern of expressed and silent genes must be restored. This restoration might be governed by mass action, determined by the binding affinities and concentrations of individual components. Alternatively, a subset of factors might remain bound to mitotic chromosomes, providing a molecular bookmark to direct proper chromatin reassembly. Here we analyse DNA at transcription start sites during mitosis invivo and find that it is conformationally distorted in genes scheduled forreactivation but is undistorted in repressed genes. Theseprotein-dependent conformational perturbations could help to re-establish transcription after mitosis by ‘marking’ genes for re-expression.

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Figure 1: Conformational distortion of the TATA-box region of the c-myc, hsp70, and β-globin genes is mitosis-specific and correlates with expression.
Figure 2: a, The c-myc P2 TATA-box region is not conformationally perturbed during mitosis when not expressed in IMR32 nucleoblastoma cells.
Figure 3: The ets-2 start site is marked during mitosis.
Figure 4: Protein requirement forthe melting of the c-myc P2 TATA-box region during mitosis.

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Acknowledgements

We thank L. Liotta, C. Wu, S. Mackem and M. Reitman for critical review of the manuscript.

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  1. Gene Regulation Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Building 10, Room 2N105, Bethesda, 20892, Maryland, USA

    Emil F. Michelotti, Suzanne Sanford & David Levens

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Michelotti, E., Sanford, S. & Levens, D. Marking of active genes on mitotic chromosomes. Nature 388, 895–899 (1997). https://doi.org/10.1038/42282

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