The Other Codes on DNA: It’s not all about codons!DNA Sequence ArchitectureDNA packaging in eukaryotesElectron Microscopy of Higher Order StructuresAFM Images of the NucleosomeAtomic-Level Structure of the NucleosomeDNA Physical ArchitectureMeasurements of Equilibrium AccessibilityLinear beam theorySlide 10Measuring the flexural rigidityEvolution of Nucleomal Positioning SequencesThe Role of DNA SequenceNucleosomes Care About PositioningConsequences of Nucleosome PositioningDNA in a Tight Squeeze: DNA Bending is UbiquitousThe Chromosome as a Polymer BlobThe Other Codes on DNA: It’s not all The Other Codes on DNA: It’s not all about codons!about codons!Small changes in the architecture of these regulatory regions can lead to dramatic phenotypic changes.Very inspiring work by Sean Carroll and David Kingsley.Quantitative data demands quantitative models!Species Genome size% coding sequencesC. elegans 100 MB 14D. melanogaster 175 MB <10Homo sapiens 2.9 GB 1.2A. Thaliana ~145 MB 21Setty 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 Order Electron Microscopy of Higher Order StructuresStructuresAFM Images of the NucleosomeAFM Images of the NucleosomeThis image was obtained with purified chromatin fragments from chicken erythroid, using the cryo-AFM. It is seen that all the linker DNA is resolved directly, and the lateral dimensions of the nucleosome are similar to those determined by electron microscopy, and are only slightly greater than that from crystallography. The resolution her eis generally higher than that at room temperature. This was at low salt. The orientation of the nucleosomes appears to be random. With this purification (low salt), linker histones are supposed to be retained.Atomic-Level Structure of the Atomic-Level Structure of the NucleosomeNucleosomeDNA DNA PhysicalPhysical Architecture ArchitecturePBOCMeasurements of Equilibrium Measurements of Equilibrium AccessibilityAccessibility(Anderson and Widom)Linear beam theoryLinear beam theoryLinear beam theoryLinear beam theoryMeasuring the flexural rigidityMeasuring the flexural rigidityTracking the equilibrium polymerWiggins et al.Show buckling movie by DogteromEvolution of Nucleomal Positioning Evolution of Nucleomal Positioning SequencesSequencesLowary 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 Nucleosome Consequences of Nucleosome PositioningPositioning(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 just transcriptional regulation!Viral DNApackagingGeneRegulationEukaryotic DNAPackagingBustamante et al.David GoodsellThe Chromosome as a Polymer BlobThe Chromosome as a Polymer
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