The global relationship between chromatin physical topology, fractal structure, and gene expression

Luay M Almassalha, A Tiwari, P T Ruhoff, Yolanda Stypula-Cyrus, Lusik Cherkezyan, H Matsuda, M A Dela Cruz, John E Chandler, Charles C White, C Maneval, Hariharan Subramanian, Igal Szleifer, Hemant K Roy, Vadim Backman

Research output: Contribution to journalJournal articleResearchpeer-review

215 Downloads (Pure)


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.

Original languageEnglish
JournalScientific Reports
Pages (from-to)41061
Number of pages13
Publication statusPublished - 24. Jan 2017

Fingerprint Dive into the research topics of 'The global relationship between chromatin physical topology, fractal structure, and gene expression'. Together they form a unique fingerprint.

Cite this