Stability and flexibility of epigenetic gene regulation in mammalian development

W Reik - Nature, 2007 - nature.com
Nature, 2007nature.com
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 …
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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