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Histone hypomethylation is an indicator of epigenetic plasticity in quiescent lymphocytes

Baxter, Jonathan, Sauer, Stephan, Peters, Antoine, John, Rosalind Margaret, Williams, Ruth, Caparros, Marie-Laure, Arney, Katharine, Otte, Arie, Jenuwein, Thomas, Merkenschlager, Matthias and Fisher, Amanda G. 2004. Histone hypomethylation is an indicator of epigenetic plasticity in quiescent lymphocytes. EMBO Journal 23 (22) , pp. 4462-4472. 10.1038/sj.emboj.7600414

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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 HP1β 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 HP1β 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: European Molecular Biology Organization; Nature Publishing Group
ISSN: 0261-4189
Last Modified: 04 Jun 2017 06:39

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