IPLS/BioP Webinar: Dr. Aakash Basu (Johns Hopkins University)

Abstract: Mechanical deformations of DNA are a ubiquitous part of universal biological processes involved in the transduction, replication, packaging, and maintenance of genetic information. However, the lack of high-throughput tools to directly measure the mechanical properties of DNA limits our understanding of whether and how DNA sequence modulates DNA mechanics and associated chromatin transactions genome-wide. We developed an assay called ‘loop-seq’ to measure DNA bendability in high throughput. In loop-seq, we selectively eliminate less bendable sequences from a large DNA library by enzymatically digesting molecules that fail to rapidly cyclize. We calculate the survival probability of every sequence in the library, which is a measure of bendability, via deep sequencing.

Using loop-seq, we constructed the first experimentally determined chromosome-wide map of any DNA physical property. The map reveals fundamental roles of sequence-encoded DNA mechanics in regulating chromatin dynamics. We provide evidence that DNA mechanics influences (i) genome-wide nucleosome organization, (ii) the activities of chromatin remodelling enzymes, (ii) RNA polymerase translocation through nucleosomes, and (iv) the evolution of codon selection in genes. We further find that epigenetic modifications such as CpG methylation alter DNA mechanics, with significant consequences for chromatin organization. Overall, this first genome-scale map of DNA mechanics hints at a ‘mechanical code’ with broad functional implications.

Host: Bart Hoogenboom (b.hoogenboom@ucl.ac.uk)
 
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