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Novel genetic and epigenetic alterations in ... - Ous-research.no

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IntroductionFigure 3. Methylation effect on chromat<strong>in</strong>. In an expressed state, the chromat<strong>in</strong> structure <strong>in</strong> proximity tothe gene is loosely packed, a state recognized by acetylation of the histone tails (i). The add<strong>in</strong>g of methyl groupsto the CpG sites (ii) is associated with a more densely packed chromat<strong>in</strong> <strong>and</strong> can be obta<strong>in</strong>ed <strong>in</strong> several ways. Afamily of prote<strong>in</strong>s with a methyl-b<strong>in</strong>d<strong>in</strong>g doma<strong>in</strong> (MBD) b<strong>in</strong>ds to the DNA-bound methyl groups. Depend<strong>in</strong>gon which prote<strong>in</strong> that b<strong>in</strong>ds, the b<strong>in</strong>d<strong>in</strong>g partners <strong>and</strong> the effects vary slightly (iii – v). The net effect is thatRNA transcription is impaired due to block<strong>in</strong>g of transcription factors, either by <strong>in</strong>hibit<strong>in</strong>g the direct b<strong>in</strong>d<strong>in</strong>g(vi) or by condensation of the chromat<strong>in</strong> structure (vii).17

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