Nature Cell Biology 8, 532 - 538 (2006)
Published online: 29 March 2006; | doi:10.1038/ncb1403
Chromatin signatures of pluripotent cell linesVéronique Azuara1, 2, Pascale Perry1, Stephan Sauer1, Mikhail Spivakov1, Helle F. Jørgensen1, Rosalind M. John1, 3, Mina Gouti1, 4, Miguel Casanova5, Gary Warnes6, Matthias Merkenschlager1
& Amanda G. Fisher11
Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK. 2
Current address: Stem Cell Initiative, Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK. 3
Current addres: Cardiff School of Biosciences, Cardiff CF10 3US, UK. 4
Current address: Developmental Biology Laboratory, Foundation for Biomedical Research of the Academy of Athens, Soranou Ephessiou 4, Athens 11527, Greece. 5
Developmental Epigenetics Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK. 6
FACS Laboratory, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Correspondence should be addressed to Véronique Azuara v.azuara@imperial.ac.uk or Amanda G. Fisher amanda.fisher@csc.mrc.ac.uk EedOct4Rex1IkarosSox1Myf5Mash1Irx3Math1Msx1Nkx2–2Nkx2–9Pax3Sox2Hoxa1Epigenetic genome modifications are thought to be important for specifying the lineage and developmental stage of cells within a multicellular organism. Here, we show that the epigenetic profile of pluripotent embryonic stem cells (ES) is distinct from that of embryonic carcinoma cells, haematopoietic stem cells (HSC) and their differentiated progeny. Silent, lineage-specific genes replicated earlier in pluripotent cells than in tissue-specific stem cells or differentiated cells and had unexpectedly high levels of acetylated H3K9 and methylated H3K4. Unusually, in ES cells these markers of open chromatin were also combined with H3K27 trimethylation at some non-expressed genes. Thus, pluripotency of ES cells is characterized by a specific epigenetic profile where lineage-specific genes may be accessible but, if so, carry repressive H3K27 trimethylation modifications. H3K27 methylation is functionally important for preventing expression of these genes in ES cells as premature expression occurs in embryonic ectoderm development (Eed)-deficient ES cells. Our data suggest that lineage-specific genes are primed for expression in ES cells but are held in check by opposing chromatin modifications.
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