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Published byClaude Allen Modified over 9 years ago
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Genomes are larger due to less gene density -Introns dilute density -Intergenetic regions dilute density -Bacteria use one intergenetic region to regulate several correlated genes. In humans only ~5% of transcribed DNA gets translated - 95% consists of introns
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DNA is wrapped around histones to form a nucelosome - first step of DNA packaging Packaging: -Allows DNA to fit into a cell (reduces length 10,000X) -Protects DNA -Makes transmission to daughter cells possible -Restricts transcription -Nucleosomes only reduce length 6x -Highly conserved structure in eukaryotes
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2 copies of 4 sub units make a histone core -Each histone protein has an N- terminal tail that is not necessary for nucleosome formation -Proteins are lysine and argenine rich - positively charged
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“Histone fold” domain assists in self assembly of tetramers and dimers -Each histone core protein has 3 alpha- helices separated by an unstructured loop -Nucleosome assembly is initiated by H3/H4 tetramer binding, followed by two H2A/H2B dimers -~40 hydrogen bonds are formed between histone proteins and the DNA backbone and minor groove -Helices fit into major groove, associate with DNA due to electrostatic charges
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Functionally, why is it important that histones only interact with the phosphate backbone and the minor groove of DNA? - There is no sequence specific binding: Nucleosomes can form with any stretch of DNA (if it hasn’t been modified in some way)
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Nucleosomes alter linkage number locally and facilitate unwinding
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Histone 1 coils DNA tighter H1 absent H1 present
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Angles of DNA entry and exit from nucleosomes generates a 30nm fiber of DNA Larger structure formation is also dependent on histone tails
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Packaging into nucleosomes and 30nm fibers shorten DNA 40x - Need to shorten 1,000-10,000x to fit into a nucleus
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DNA is looped into a nuclear scaffold - 1 loop is 40-90kb
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Histone tails may be modified to allow easier access to DNA
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