Histone hypomethylation is an indicator of epigenetic plasticity in quiescent lymphocytes.
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 (G(0)) 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.
Baxter
Jonathan
J
Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Sauer
Stephan
S
Peters
Antoine
A
John
Rosalind
R
Williams
Ruth
R
Caparros
Marie-Laure
ML
Arney
Katharine
K
Otte
Arie
A
Jenuwein
Thomas
T
Merkenschlager
Matthias
M
Fisher
Amanda G
AG
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D015153:Blotting, Western; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D020868:Gene Silencing; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D008745:Methylation; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D011496:Protein Methyltransferases; D016192:Resting Phase, Cell Cycle; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000502:physiology*; D015854:Up-Regulation
D002843:Chromatin; D006657:Histones; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine