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Chromatin signatures of pluripotent cell lines

Item Type:Article
Title:Chromatin signatures of pluripotent cell lines
Creators Name:Azuara, V. and Perry, P. and Sauer, S. and Spivakov, M. and Jorgensen, H.F. and John, R.M. and Gouti, M. and Casanova, M. and Warnes, G. and Merkenschlager, M. and Fisher, A.G.
Abstract: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.
Keywords:Carcinoma, Cell Line, Chromatin, Cultured Cells, DNA Replication Timing, Down-Regulation, Gene Expression Profiling, Genetic Epigenesis, Genetic Markers, Hematopoietic Stem Cells, Multipotent Stem Cells, Pluripotent Stem Cells, Polycomb Repressive Complex 2, Repressor Proteins, T-Lymphocytes, Animals, Mice
Source:Nature Cell Biology
Publisher:Nature Publishing Group
Page Range:532-538
Date:May 2006
Official Publication:https://doi.org/10.1038/ncb1403
PubMed:View item in PubMed

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