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  • The EMBO Journal (2004) 23, 4462 - 4472
  • doi:10.1038/sj.emboj.7600414

Published online: 28 October 2004

Histone hypomethylation is an indicator of epigenetic plasticity in quiescent lymphocytes

Jonathan Baxter1,a, Stephan Sauer1,a, Antoine Peters2, Rosalind John1, Ruth Williams1, Marie-Laure Caparros1, Katharine Arney1, Arie Otte3, Thomas Jenuwein2, Matthias Merkenschlager1 and Amanda G Fisher1

  1. Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, UK
  2. Research Institute of Molecular Pathology (IMP), Vienna Biocenter, Vienna, Austria
  3. Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Netherlands

Correspondence to:

Amanda G Fisher, Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. Tel.: +44 208 383 8238/39; Fax: +44 208 383 8338; E-mail: amanda.fisher@csc.mrc.ac.uk

aThese two authors contributed equally to this work

Received 29 September 2003; Accepted 20 August 2004

Post-translational modifications of histone amino termini are thought to convey epigenetic information that extends the coding potential of DNA. In particular, histone lysine methylation has been implicated in conveying transcriptional memory and maintaining lineage fidelity. Here an analysis of histone lysine methylation in quiescent (G0) and cycling lymphocytes showed that methylation of histone H3 at lysines 4 (H3K4), 9 (H3K9), 27 (H3K27) and histone H4 at lysine 20 is markedly reduced in resting B lymphocytes as compared with cycling cells. Quiescent B cells also lacked heterochromatin-associated HP1beta and Ikaros at pericentric chromatin and expressed low levels of Ezh2 and ESET histone methyl transferases (HMTases). Nuclei from resting B or T cells were approximately three times more efficiently reprogrammed in nuclear transfer assays than cells in which HMTase expression, histone methylation and HP1beta binding had been restored following mitotic stimulation. These results showing local and global changes in histone lysine methylation levels in vivo demonstrate that constitutive heterochromatin organization is modified in resting lymphocytes and suggest that histone hypomethylation is a useful indicator of epigenetic plasticity.

  • Keywords:

    • histone,
    • lymphocytes,
    • methylation,
    • reprogramming