Deciphering the Gene Regulatory Landscape Encoded in DNA Biophysical Features
| Autor: | Jan Lipfert, Vijay K. Tiwari, Abhijeet Pataskar, Willem Vanderlinden, Johannes Friedrich Emmerig, Aditi Singh |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Biophysics 02 engineering and technology Computational biology Biology ENCODE Article Molecular Genetics 03 medical and health sciences chemistry.chemical_compound Molecular genetics Genetics medicine natural sciences Epigenetics General lcsh:Science Gene Transcription factor Regulation of gene expression Multidisciplinary 021001 nanoscience & nanotechnology Phenotype 030104 developmental biology chemistry lcsh:Q 0210 nano-technology DNA |
| Zdroj: | iScience, Vol 21, Iss, Pp 638-649 (2019) iScience Pataskar, A, Vanderlinden, W, Emmerig, J, Singh, A, Lipfert, J & Tiwari, V K 2019, ' Deciphering the Gene Regulatory Landscape Encoded in DNA Biophysical Features ', iScience, vol. 21, pp. 638-649 . https://doi.org/10.1016/j.isci.2019.10.055 |
| ISSN: | 2589-0042 |
| Popis: | Summary Gene regulation in higher organisms involves a sophisticated interplay between genetic and epigenetic mechanisms. Despite advances, the logic in selective usage of certain genomic regions as regulatory elements remains unclear. Here we show that the inherent biophysical properties of the DNA encode epigenetic state and the underlying regulatory potential. We find that the propeller twist (ProT) level is indicative of genomic location of the regulatory elements, their strength, the affinity landscape of transcription factors, and distribution in the nuclear 3D space. We experimentally show that ProT levels confer increased DNA flexibility and surface accessibility, and thus potentially primes usage of high ProT regions as regulatory elements. ProT levels also correlate with occurrence and phenotypic consequences of mutations. Interestingly, cell-fate switches involve a transient usage of low ProT regulatory elements. Altogether, our work provides unprecedented insights into the gene regulatory landscape encoded in the DNA biophysical features. Graphical Abstract Highlights • DNA shape features encode genomic surface accessibility and flexibility • High ProT is a deterministic feature of enhancers • ProT levels correlate with nuclear organization of epigenetic states • Cell-fate switches involve a transient usage of low ProT regulatory elements Genetics; Molecular Genetics; Biophysics |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|