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The Other Codes on DNA: It’s not all about codons! Small changes in the architecture of these regulatory regions can lead to dramatic phenotypic changes.

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Presentation on theme: "The Other Codes on DNA: It’s not all about codons! Small changes in the architecture of these regulatory regions can lead to dramatic phenotypic changes."— Presentation transcript:

1 The Other Codes on DNA: It’s not all 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 sequences C. elegans100 MB14 D. melanogaster175 MB<10 Homo sapiens2.9 GB1.2 A. Thaliana~145 MB21 Setty et al. (2003) Small et al. (1992, 1996) Elowitz et al. (2000) How much? When? Where? Shapiro and von Sternberg (2005)

2 DNA Sequence Architecture PBOC FlyEx Small et al. (1996)

3 DNA packaging in eukaryotes

4 Electron Microscopy of Higher Order Structures

5 AFM Images of the Nucleosome This 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.

6 Atomic-Level Structure of the Nucleosome

7 DNA Physical Architecture PBOC

8 Measurements of Equilibrium Accessibility (Anderson and Widom)

9 Linear beam theory

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11 Measuring the flexural rigidity Tracking the equilibrium polymer Wiggins et al. Show buckling movie by Dogterom

12 Evolution of Nucleomal Positioning Sequences Lowary and Widom

13 The Role of DNA Sequence (Cloutier and Widom)

14 Nucleosomes Care About Positioning (Segal et al.)

15 Consequences of Nucleosome Positioning (Segal et al.)

16 DNA in a Tight Squeeze: DNA Bending is Ubiquitous Understanding tightly bent DNA goes beyond just transcriptional regulation! Viral DNA packaging Gene Regulation Eukaryotic DNA Packaging Bustamante et al. David Goodsell

17 The Chromosome as a Polymer Blob b=2P


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