Chromatin signatures of pluripotent cell lines.
Epigenetic 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.
Azuara
Véronique
V
Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK. v.azuara@imperial.ac.uk
Perry
Pascale
P
Sauer
Stephan
S
Spivakov
Mikhail
M
Jørgensen
Helle F
HF
John
Rosalind M
RM
Gouti
Mina
M
Casanova
Miguel
M
Warnes
Gary
G
Merkenschlager
Matthias
M
Fisher
Amanda G
AG
D000818:Animals; D002277:Carcinoma / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics*; D042522:DNA Replication Timing / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D051379:Mice; D039902:Multipotent Stem Cells / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2; D012097:Repressor Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
D002843:Chromatin; C107275:Eed protein, mouse; D005819:Genetic Markers; D012097:Repressor Proteins; D063151:Polycomb Repressive Complex 2