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The physical properties of DNA encode genetic information

Aakash Basu
Johns Hopkins School of Medicine | Postdoctoral Research Fellow, Department of Biophysics & Biophysical Chemistry
Seminar date:
Wednesday, February 17, 2021 - 12:00 to 13:00

Mechanical deformations of DNA are ubiquitously part of universal biological processes involved in the transduction of genetic information. Although the average compliance of DNA to accommodate such deformations has been extensively measured, biophysical measurements of DNA have never been conducted on a genome-wide scale. Consequently, we lack experimental understanding of the extent to which the local mechanical properties of DNA vary with sequence along entire genomes, and how such variations modulate the energetics of diverse biological processes. By combining DNA cyclization with deep sequencing, we developed a method called ‘loop-seq’ to measure the bendabilities of ~100,000 50 bp DNA fragments at a time. Using loop-seq, we established the first experimentally derived chromosome-wide map of any DNA physical property and showed that DNA bendability is genetically encoded to a significant extent. We found that sequence-encoded modulations in bendability influence nucleosome arrangements from promoters to deep within gene bodies and serve as physical landmarks guiding chromatin remodeling enzymes. We also found that DNA mechanics impacts transcription, transcription factor binding, and topoisomerase action, and that innate mechanics associated with sequence is modulated by epigenetic modifications. Finally, our data suggest that pressure to preserve functionally important mechanical modulations along DNA has impacted the evolution of codon choice in yeast genes. Overall, our results indicate that a novel form of genetic information, with broad regulatory impact, is encoded in the physical properties of DNA.

Fields of interest: