The Global Relationship between Chromatin Physical Topology, Fractal Structure, and Gene Expression
Year: 2017
Type: article
Abstract: Most of what we know about gene transcription comes from the view of cells as molecular machines: focusing on the role of molecular modifications to the proteins carrying out transcriptional reactions at a loci-by-loci basis. This view ignores a critical reality: biological reactions do not happen in an empty space, but in a highly complex, interrelated, and dense nanoenvironment that profoundly influences chemical interactions. We explored the relationship between the physical nanoenvironment of chromatin and gene transcription in vitro. We analytically show that changes in the fractal dimension, D, of chromatin correspond to simultaneous increases in chromatin accessibility and compaction heterogeneity. Using these predictions, we demonstrate experimentally that nanoscopic changes to chromatin D within thirty minutes correlate with concomitant enhancement and suppression of transcription. Further, we show that the increased heterogeneity of physical structure of chromatin due to increase in fractal dimension correlates with increased heterogeneity of gene networks. These findings indicate that the higher order folding of chromatin topology may act as a molecular-pathway independent code regulating global patterns of gene expression. Since physical organization of chromatin is frequently altered in oncogenesis, this work provides evidence pairing molecular function to physical structure for processes frequently altered during tumorigenesis.
Source: Scientific Reports
DOI: 10.1038/srep41061
Authors: L. M. Almassalha, A. Tiwari, P. T. Ruhoff, Y. Stypula-Cyrus, L. Cherkezyan, H. Matsuda, M. A. Dela Cruz, J. E. Chandler, C. White, C. Maneval, H. Subramanian, I. Szleifer, H. K. Roy, V. Backman
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funders: National Science Foundation, Chicago Community Trust, Northwestern University, Chicago Biomedical Consortium, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, Division of Chemical, Bioengineering, Environmental, and Transport Systems
Awards: G1018718831, G1123447905, G1259591088, G2380330964, G2466697979, G261961061, G2815223910, Spatio-Temporal Organization of Chromatin and Information Transfer in Cancer, G3549828030, Pathophysiology of Acute Lung Injury, G39563676, Graduate Research Fellowship Program, EAGER: New Biophotonics and Computational Molecular Dynamics for Understanding Epigenetic Regulation of Gene Transcription, G818203090, G9000042048, G9000108312, G9000136738, G9000177991, G9000275401, The Robert H. Lurie Comprehensive Cancer Center
OpenAlex ID: W2581385317