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Functional genomics Part I.docx

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BIOL 3150

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Functional genomics Part I: Accessing Eukaryotic Genomes (Chapter 10) • Frequent presence of Philadelphia Chromosome in chronic myeloid leukemia suggests that chromosomes 9 and 22 occupy adjacent territories in nucleus • Active functional domains are relatively uncondensed open chromatin regions that are sensitive to DNase I digestion, condensed regions are resistant • Limited digestion of chromatin with a micrococcal nuclease results in chromatin framents with regular length intervals that correspond to number of nucleosomes = map position of nucleosomes • Eukaryotic DNAis packaged with histones into basic units call nucleosomes • Nucleosome consist of ~146bp of DNAwrapped around an octamer of histones o 2 copies of H2A, H2B, H3, H4 o Driving force for wrapping is electrostatic: + protein, - DNA o Amino-terminal tails of histones targeted by a variety of post-translation covalent modifications, which could dictate gene activity • Eukaryotic centromeres enriched with CENP-Aproteins which are variants of histone H3 • Certain histone modifications have been linked to gene activities, promoters enriched for acetylation and methylated lysine 4. • Positions of nucleosomes are highly dynamic and can rapidly alter in response to gene activity o Remodeling complexes useATP hydrolysis to regulate position of nucleosomes – can remodel, slide, transfer • Two major chromatin: o E
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