5 - Epigenetic regulation of gene expression, Bird & Jaenisch

5 - Epigenetic regulation of gene expression, Bird & Jaenisch

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Article #5 Cells of a multicellular organism are genetically homogeneous, but structurally and functionally heterogeneous b/c of different gene expression Epigenetics or “outside conventional genetics” - describes the study of stable alterations in gene expression potential that arise during development & cell proliferation Such epigenetic processes are essential for development & differentiation, but they can also arise in mature humans & mice, either by random change or under environ influence also guard against viral genomes that would otherwise hijack cellular fn modification of DNA or proteins are recognized by specific proteins that recognize modifications and facilitate the appropriate biological effects Establishing and maintaining patterns of DNA methylation DNA methylation o chief contributor to stability of gene expression states, might be responsible for stable maintenance of particular gene expression pattern through mitotic cell division and is involved in maintaining X chromosome inactivation in females o DNA methylation est. a silent chromatin state by collaborating with protein that modify nucleosomes o Post replication modification o DNA methylation found in cytosines of the dinucleotide sequence CpG Extent of DNA methylation changes during mammalian development: o Wave of demethylation during cleavage o Genome wide methylation after implantation o Demethylation is an active process that strips the male genome of methylation within hours of fertilization. o Maternal genome is only passively demethylated during cleavage divisions o methylation decreases in specific tissues during differentiation o methylation occurs rarely in postgastrulation – but is seen in cancer! DNA methyltransferases (DNMT): DNMT1 maintenance methylrtansferase (i.e. maintains but not est maternal imprint), absence results in global demethylation and embryonic lethality, DNMT1o responsible for maintaining, but not establishing maternal imprints DNMT3a, DNMT3b methylation after implantation, expressed highly during developing embryo DNMT3L no DNMT activity on own but joins to DNMT3a/b to imprint on female germ line
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DNMT2 no DNMT alone, may be responsible for small amount of non-Cpg methylation in flied DNA meth is essential for vertebrate development Loss of methylation causes apoptosis in embryos/fibroblasts, NOT in stem cells, or cancer cells, depression of extopic gene expression, and transcriptional
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5 - Epigenetic regulation of gene expression, Bird & Jaenisch

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