The Other Codes on DNA: ItThe Other Codes on DNA: It’’s not alls not allabout about codonscodons!!Small changes in the architecture of theseregulatory regions can lead to dramaticphenotypic changes.Very inspiring work by Sean Carroll and DavidKingsley.Quantitative data demands quantitativemodels!21~145 MBA. Thaliana1.22.9 GBHomo sapiens<10175 MBD. melanogaster14100 MBC. elegans% codingsequencesGenomesizeSpeciesSetty et al. (2003)Small et al. (1992, 1996)Elowitz et al. (2000)How much?When?Where?Shapiro and von Sternberg (2005)DNA DNA SequenceSequence Architecture ArchitecturePBOCFlyExSmall et al. (1996)DNA packaging in eukaryotesDNA packaging in eukaryotesElectron Microscopy of Higher OrderElectron Microscopy of Higher OrderStructuresStructuresAFM Images of the NucleosomeAFM Images of the NucleosomeThis image was obtained with purified chromatin fragments from chicken erythroid, usingthe cryo-AFM. It is seen that all the linker DNA is resolved directly, and the lateraldimensions of the nucleosome are similar to those determined by electron microscopy, andare only slightly greater than that from crystallography. The resolution her eis generallyhigher than that at room temperature. This was at low salt. The orientation of thenucleosomes appears to be random. With this purification (low salt), linker histones aresupposed to be retained.Atomic-Level Structure of theAtomic-Level Structure of theNucleosomeNucleosomeDNA DNA PhysicalPhysical Architecture ArchitecturePBOCMeasurements of EquilibriumMeasurements of EquilibriumAccessibilityAccessibility(Anderson and Widom)Linear beam theoryLinear beam theoryLinear beam theoryLinear beam theoryMeasuring the flexural rigidityMeasuring the flexural rigidityTracking theequilibrium polymerWiggins et al.Show bucklingmovie by DogteromEvolution of Evolution of NucleomalNucleomal Positioning PositioningSequencesSequencesLowary and WidomThe Role of DNA SequenceThe Role of DNA Sequence(Cloutier and Widom)Nucleosomes Care About PositioningNucleosomes Care About Positioning(Segal et al.)Consequences of NucleosomeConsequences of NucleosomePositioningPositioning(Segal et al.)DNA in a Tight Squeeze:DNA in a Tight Squeeze:DNA Bending is UbiquitousDNA Bending is UbiquitousUnderstanding tightly bent DNA goes beyond justtranscriptional regulation!Viral DNApackagingGeneRegulationEukaryotic DNAPackagingBustamante et al.David GoodsellThe Chromosome as a Polymer BlobThe Chromosome as a Polymer
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