Epigenetic regulation starts with DNA wound around a set of completely acetylated histones associated with an activated, fully transcribed gene. Transcriptional repression is initiated by deacetylating multiple lysine residues of histone proteins near the promoter. These lysines can be methylated up to three times per lysine, each time resulting in gene shutdown. Also, the cytosines in the gene can be methylated at their 5' carbon. Each modification in this chain from acetylation to DNA methylation is associated with a compaction of the gene into dense, untranscribable chromatin.
DNA methylation, histone modifications, and changes to higher-order chromatin structure play a central role in the regulation of mammalian genome organization. The epigenetic signature of any cell provides valuable information about its cellular state, its developmental potential, and its overall health.
DNA methylation is a normally occurring modification in both eukaryotic and prokaryotic organisms. In many plants and animals, it is characterized by the biochemical addition of a methyl group (–CH3) to the cytosine C5 in cytosinephosphate-guanine (CpG) dinucleotides via a methyltransferase enzyme. In plants, the cytosine can be methylated in the CpG, CpNpG, and CpNpN contexts, where N represents any base except guanine. Bacteria tend to methylate adenosine.
The majority of CpG dinucleotides in the mammalian genome are methylated (5-methylcytosine). Those that are unmethylated typically reside in so called CpG islands, or G+C-rich regions >300 bp in length where the observed to expected ratio of CpG is >0.6. CpG islands typically reside at the 5' ends of genes, and the majority of all human genes have CpG islands at their 5' end. When CpG islands become aberrantly hypermethylated, it is generally associated with decreased expression of the gene. DNA methylation is an epigenetic event that is involved in embryonic development and cell cycle regulation; hence analyzing DNA methylation is necessary for understanding gene expression.
DNA methylation.A methyl group addition to the cytosine carbon 5 in cytosine-phosphate-guanine (CpG) and other nucleotide sequences inhibits the binding of transcription factors to promoters.
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