Epigenetic Tags
Gene expression can be controlled by epigenetic tags which function to switch genes ‘on' (active) or ‘off’ (inactive)
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In eukaryotes, these tags can either be added to the DNA directly or be added to the histone proteins responsible for packaging the DNA
DNA Methylation
DNA methylation involves the incorporation of a methyl group to a DNA base in order to change the activity of a DNA segment without changing the base sequence
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In eukaryotes, DNA methylation predominantly occurs at cytosine bases that are immediately adjacent to a guanine base (called a CpG island)
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This results in two methyl groups positioned diagonally to each other on opposing DNA strands (as G and C are complementary base partners)
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A majority of eukaryotic genes have CpG islands within their promoter sequence and the direct methylation of the promoter impedes the activity of RNA polymerase
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Hence DNA methylation functions to reduce transcriptional activity in eukaryotic cells by inactivating transcription (gene is switched ‘off’)
High CpG methylation in eukaryotic genomes may have an evolutionary cost because it increases the frequency of spontaneous mutations (methylated cytosines can deaminate to form thymine)
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In many diseases (including cancer), gene promoters become hypermethylated – resulting in transcriptional silencing of essential genes (such as tumor suppressor genes)
Histone Methylation
In eukaryotic organisms, the DNA is associated with histone proteins to form a condensed complex known as a nucleosome
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These histone proteins have protruding tails that are positively charged, which allows the histone to associate with the negatively charged DNA
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Adding an acetyl group to the tail (acetylation) neutralises the charge, making DNA less tightly coiled and increasing transcription
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Adding a methyl group to the tail (methylation) maintains the positive charge, making DNA more coiled and reducing transcription
Types of Chromatin
Individual nucleosomes are linked together (like beads on a string) to form chromatin (the unravelled form of a eukaryotic chromosome)
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When DNA is supercoiled (tightly packed) and not accessible for transcription, it exists as condensed heterochromatin
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When the DNA is loosely packed and therefore accessible to the transcription machinery, it exists as euchromatin
Different cell types will have varying segments of DNA packaged as heterochromatin and euchromatin depending on which genes are active within the cell
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Some segments of DNA may be permanently supercoiled, while other segments may change over the life cycle of the cell