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Related Experiment Videos

Histone code modifications on pluripotential nuclei of reprogrammed somatic cells.

Hironobu Kimura1, Masako Tada, Norio Nakatsuji

  • 1Department of Development and Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.

Molecular and Cellular Biology
|June 26, 2004
PubMed
Summary

Somatic cell reprogramming by embryonic stem (ES) cells leads to epigenetic changes. Histone modifications like hyperacetylation and H3 lysine 4 (K4) methylation occur, creating a permissive state for gene activation.

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Area of Science:

  • Epigenetics
  • Cell Biology
  • Genomics

Background:

  • Somatic genome reprogramming by embryonic stem (ES) cells confers pluripotency.
  • Epigenetic modifications, including histone acetylation and methylation, are crucial for cell-type-specific epigenotype memory.
  • Histone H3 and H4 amino-terminal modifications regulate gene activity via chromatin conformation.

Purpose of the Study:

  • To investigate the epigenetic modifications occurring in the somatic genome during ES cell-mediated reprogramming.
  • To determine the role of histone modifications, specifically acetylation and H3 lysine 4 (K4) methylation, in establishing a pluripotent state.
  • To analyze the correlation between these epigenetic marks and gene activation in reprogrammed cells.

Main Methods:

  • Hybridization of somatic cells with ES cells to induce reprogramming.

Related Experiment Videos

  • Analysis of histone modifications (acetylation and methylation at H3 and H4) in reprogrammed somatic genomes.
  • Promoter region analysis of specific genes (Oct4, Neurofilament-M, Nfl, Thy-1) to assess epigenetic marks and gene activity.

    • Main Results:

    • Reprogrammed somatic genomes in ES hybrid cells exhibit global hyperacetylation of histones H3 and H4.
    • Global di- and tri-methylation at H3 lysine 4 (K4) is observed in reprogrammed somatic genomes.
    • While H3-K4 tri-methylation correlates with activation of Oct4 and DNA demethylation, it is also present in silent gene promoters (Nfm, Nfl, Thy-1).

    Conclusions:

    • H3-K4 di- and tri-methylation during somatic genome reprogramming is independent of immediate gene activity.
    • These methylation events are key components of the reprogramming process, establishing a transcriptional activation-permissive state.
    • Epigenetic reprogramming by ES cells involves significant histone modifications essential for pluripotency acquisition.