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      Stability and flexibility of epigenetic gene regulation in mammalian development.

      Nature

      genetics, embryology, Mammals, Genomic Imprinting, Gene Silencing, Gene Expression Regulation, Developmental, Epigenesis, Genetic, DNA Transposable Elements, Animals

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          Abstract

          During development, cells start in a pluripotent state, from which they can differentiate into many cell types, and progressively develop a narrower potential. Their gene-expression programmes become more defined, restricted and, potentially, 'locked in'. Pluripotent stem cells express genes that encode a set of core transcription factors, while genes that are required later in development are repressed by histone marks, which confer short-term, and therefore flexible, epigenetic silencing. By contrast, the methylation of DNA confers long-term epigenetic silencing of particular sequences--transposons, imprinted genes and pluripotency-associated genes--in somatic cells. Long-term silencing can be reprogrammed by demethylation of DNA, and this process might involve DNA repair. It is not known whether any of the epigenetic marks has a primary role in determining cell and lineage commitment during development.

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          Journal
          10.1038/nature05918
          17522676

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