Chromatin - a general transcriptional repressor

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  • Chromatin - a general transcriptional repressor
    • The N-terminal tails of histones are free to be modified to activate transcription
    • Active chromatin is in different conformation to inactive
      • Active regions sensitive to cleavage by DNase I - hyper DNase sensitive sites as are nucleosome free
        • E.g. enhancer regions of genes ready for transcription
        • E.g. globin gene locus in pre-erythroid cells is DNase sensitive in some cells but DNase resistant in others where globin is not transcribed
    • Different forms of chromatin
      • Heterochromatin
        • Highly condensed throughout cell cycle
        • Highly repetitive 'junk' DNA
        • Transcriptionally silent genes
        • Enriched in methylcytosine
        • Histones underacetylated
      • Euchromatin
        • DNA decondensed during interphase
        • Most genes
        • Transcriptionally active genes
        • Sensitive to DNAse I digestion
      • Facultative heterochromatin
        • Switches depending on what is needed
    • Position effect variation (PEV)
      • Moving genes from heterochromatin -> euchromatin is associated with changes in gene expression - e.g. moving trans genes into heterochromatin; gene won't be expressed (see dolly da sheep!)

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