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Patho-Epigenetics of Disease (Paperback, 2012 ed.)
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Patho-Epigenetics of Disease (Paperback, 2012 ed.)
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In multicellular organisms the establishment, maintenance, and
programmed alterations of cell-type specific gene expression
patterns are regulated by epigenetic mechanisms. Thus, epigenetic
alterations (DNA methylation, DNA associated Polycomb-Trithorax
protein complexes, histone modifications) ensure the unique
transcriptional activity and phenotypic diversity of diploid cells
that carry identical or nearly identical DNA sequences. Because DNA
methyltransferase I (DNMT1) associates with replication foci during
S phase and prefers hemimethylated DNA as a substrate, DNMT1
ensures the clonal propagation of cytosine methylation patterns
(maintenance methylation). Thus, DNA methylation may provide a
memory function by helping progeny cells to "remember" their proper
cellular identity. An alternative system of epigenetic memory, the
Polycomb and Trithorax groups of protein complexes, that may
operate both independently from and in concert with DNA
methylation, ensures the heritable regulation of gene expression
via modification of histone tails. The complex interplay of
epigenetic regulatory mechanisms permits both the dynamic
modulation of gene expression and the faithful transmission of gene
expression patterns to each progeny cell upon division. These
carefully orchestrated processes can go wrong, however, resulting
in epigenetic reprogramming of the cells that may manifest in
pathological changes, as it was first realized during the studies
of epigenetic alterations in malignant tumors. By now it became a
well established fact that not only genetic changes, but also the
disruption of epigenetic regulation can result in carcinogenesis
and tumor progression. Scientists working in other fields soon
followed the pioneering work of cancer researchers, and revealed
that epigenetic dysregulation forms the basis of a wide spectrum of
human diseases.
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