• Open Access

Programming the genome in embryonic and somatic stem cells

Authors

  • Philippe Collas,

    Corresponding author
    1. Institute of Basic Medical Sciences, Department of Biochemistry, Faculty of Medicine, University of Oslo, Norway
      *Correspondence to: Professor Philippe COLLAS
      Institute of Basic Medical Sciences,
      Department of Biochemistry,
      Faculty of Medicine, University of Oslo,
      PO Box 1112 Blindern, 0317 Oslo, Norway.
      Tel: +47–22 85 10 66
      Fax: +47–22 85 10 58.
      E-mail: philippe.collas@medisin.uio.no
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  • Agate Noer,

    1. Institute of Basic Medical Sciences, Department of Biochemistry, Faculty of Medicine, University of Oslo, Norway
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  • Sanna Timoskainen

    1. Institute of Basic Medical Sciences, Department of Biochemistry, Faculty of Medicine, University of Oslo, Norway
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*Correspondence to: Professor Philippe COLLAS
Institute of Basic Medical Sciences,
Department of Biochemistry,
Faculty of Medicine, University of Oslo,
PO Box 1112 Blindern, 0317 Oslo, Norway.
Tel: +47–22 85 10 66
Fax: +47–22 85 10 58.
E-mail: philippe.collas@medisin.uio.no

Abstract

  • • Introduction
  • • Epigenetic makeup of embryonic stem cells: keeping chromatin loose
    • - DNA methylation and gene expression
    • - CpG methylation profiles in mouse ESCs
    • - CpG methylation patterns in human ESCs
    • - Both active and inactive histone modification marks on developmentally regulated genes in ESCs suggest transcriptional activation potential
    • - A regulatory role of histone H1 in gene expression in embryonic stem cells?
    • - Polycomb group proteins impose a transcriptional brake on lineage-priming genes
  • • The epigenetic makeup of mesenchymal stem cells reflects restricted differentiation potential
    • - CpG methylation patterns on lineage-specific promoters in adipose stem cells
    • - CpG content affects the relationship between promoter DNA methylation and transcriptional activity
    • - Bivalent histone modifications on potentially active genes?
  • • Linking DNA methylation to histone modifications, chromatin packaging and (re)organization of the nuclear compartment
  • • Perspectives: towards remodelling the stem cell epigenome?

Abstract

In opposition to terminally differentiated cells, stem cells can self-renew and give rise to multiple cell types. Embryonic stem cells retain the ability of the inner cell mass of blastocysts to differentiate into all cell types of the body and have acquired in culture unlimited self-renewal capacity. Somatic stem cells are found in many adult tissues, have an extensive but finite lifespan and can differentiate into a more restricted array of cell types. A growing body of evidence indicates that multi-lineage differentiation ability of stem cells can be defined by the potential for expression of lineage-specification genes. Gene expression, or as emphasized here, potential for gene expression, is largely controlled by epigenetic modifications of DNA and chromatin on genomic regulatory and coding regions. These modifications modulate chromatin organization not only on specific genes but also at the level of the whole nucleus; they can also affect timing of DNA replication. This review highlights how mechanisms by which genes are poised for transcription in undifferentiated stem cells are being uncovered through primarily the mapping of DNA methylation, histone modifications and transcription factor binding throughout the genome. The combinatorial association of epigenetic marks on developmentally regulated and lineage-specifying genes in undifferentiated cells seems to define a pluripotent state.

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