Marking of active genes on mitotic chromosomes.
During development and differentiation, cellular phenotypes are stably propagated through numerous cell divisions. This epigenetic 'cell memory' helps to maintain stable patterns of gene expression. DNA methylation and the propagation of specific chromatin structures may both contribute to cell memory. 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 phase; second, the chromatin state must survive mitosis, when chromatin condenses, transcription is turned off, and almost all double-stranded DNA-binding proteins are displaced. 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 in vivo and find that it is conformationally distorted in genes scheduled for reactivation but is undistorted in repressed genes. These protein-dependent conformational perturbations could help to re-establish transcription after mitosis by 'marking' genes for re-expression.
Michelotti
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EF
Gene Regulation Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Sanford
S
S
Levens
D
D
D001483:Base Sequence; D002453:Cell Cycle; D002460:Cell Line; D002843:Chromatin / Q000502:physiology; D002877:Chromosomes, Human / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D015870:Gene Expression; D016259:Genes, myc; D005819:Genetic Markers; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000187:drug effects / Q000235:genetics*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D011196:Potassium Permanganate / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D016385:TATA Box; D014407:Tumor Cells, Cultured
D002843:Chromatin; D005819:Genetic Markers; D018840:HSP70 Heat-Shock Proteins; D011196:Potassium Permanganate; D004247:DNA