Bookmarking target genes in mitosis: a shared epigenetic trait of phenotypic transcription factors and oncogenes?

Cancer Res. 2014 Jan 15;74(2):420-5. doi: 10.1158/0008-5472.CAN-13-2837. Epub 2014 Jan 9.

Abstract

The regulatory information for phenotype, proliferation, and growth of normal and tumor cells must be maintained through genome replication in the S phase and cell division during mitosis. Epigenetic mechanisms that include DNA methylation, posttranslational modifications of histones, selective utilization of histone variants, and inheritable RNA molecules play pivotal roles in maintaining cellular identity through mitotic divisions. Recent studies demonstrate that mitotic occupancy of genes, which are determinants of cell fate, growth, and proliferation, by lineage-restricted transcription factors is a key epigenetic mechanism for retention and transmission of cellular expression memory. Evidence is emerging for the presence of distinct transcriptional regulatory microenvironments in mitotic chromosomes in which the genes bookmarked for reactivation postmitotically reside. Importantly, some oncoproteins are present in mitotic microenvironments where they occupy target genes during mitosis and may contribute to perpetuating the transformed phenotype. We discuss emerging regulatory implications of epigenetically bookmarking genes during mitosis for physiologic control as well as for the onset and progression of cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation
  • Cell Lineage
  • Cell Nucleus / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • Cohesins
  • DNA Methylation
  • Disease Progression
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Neoplastic*
  • Histones / metabolism
  • Humans
  • Mitosis*
  • Oncogenes / genetics*
  • Phenotype
  • Protein Processing, Post-Translational
  • Stem Cells / cytology
  • Transcription Factors / metabolism*

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Histones
  • Transcription Factors