Exploring cellular memory molecules marking competent and active transcriptions

BMC Mol Biol. 2007 May 10:8:31. doi: 10.1186/1471-2199-8-31.

Abstract

Background: Development in higher eukaryotes involves programmed gene expression. Cell type-specific gene expression is established during this process and is inherited in succeeding cell cycles. Higher eukaryotes have evolved elegant mechanisms by which committed gene-expression states are transmitted through numerous cell divisions. Previous studies have shown that both DNase I-sensitive sites and the basal transcription factor TFIID remain on silenced mitotic chromosomes, suggesting that certain trans-factors might act as bookmarks, maintaining the information and transmitting it to the next generation.

Results: We used the mouse globin gene clusters as a model system to examine the retention of active information on M-phase chromosomes and its contribution to the persistence of transcriptional competence of these gene clusters in murine erythroleukemia cells. In cells arrested in mitosis, the erythroid-specific activator NF-E2p45 remained associated with its binding sites on the globin gene loci, while the other major erythroid factor, GATA-1, was removed from chromosome. Moreover, despite mitotic chromatin condensation, the distant regulatory regions and promoters of transcriptionally competent globin gene loci are marked by a preserved histone code consisting in active histone modifications such as H3 acetylation, H3-K4 dimethylation and K79 dimethylation. Further analysis showed that other active genes are also locally marked by the preserved active histone code throughout mitotic inactivation of transcription.

Conclusion: Our results imply that certain kinds of specific protein factors and active histone modifications function as cellular memory markers for both competent and active genes during mitosis, and serve as a reactivated core for the resumption of transcription when the cells exit mitosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Cell Line, Tumor
  • Chromosomes, Mammalian / metabolism
  • Epigenesis, Genetic
  • GATA1 Transcription Factor / metabolism*
  • Globins / genetics*
  • Histones / metabolism
  • Methylation
  • Mice
  • Mitosis*
  • NF-E2 Transcription Factor, p45 Subunit / metabolism*
  • Promoter Regions, Genetic
  • Transcriptional Activation*

Substances

  • GATA1 Transcription Factor
  • Gata1 protein, mouse
  • Histones
  • NF-E2 Transcription Factor, p45 Subunit
  • Globins