Gene Structure Heterogeneity and Loop Extrusion Drive Transcriptional Noise in Human Cells

Nick Gilbert, PhD - Professor of Chromatin Biology, Medical Research Council Human Genetics Unit at the University of Edinburgh, Scotland, UK
Transcriptional noise, or heterogeneity, provides phenotypic variation within a cell population, but the molecular basis for this phenomenon is unclear. In this study we use computer simulations based on biophysical principles of genome organisation to simultaneously predict 3D structure and transcriptional output of human chromatin genome-wide. Exploration of this dataset shows that genes can adopt different 3D structures, while influential nodes within a locus control structural diversity and are linked to gene function. Furthermore, structural snapshots from within simulations show that transcription strongly correlates with the formation of protein-mediated microphase separated clusters of promoters and enhancers, and concomitantly transcriptional noise is determined by gene structure heterogeneity and loop extrusion.
The Monthly Seminar on Physical Genomics is a public lecture series sponsored by the Center for Physical Genomics at Northwestern University, the Robert H. Lurie Comprehensive Cancer Center, and NIH Grants T32GM142604 and U54CA268084. CPGE's (growing) archive of public seminars and talks can be found at:physicalgenomics.northwestern...

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