April 20, 2017

"Transcription factories: genome organization and gene regulation"

4:00 PM to 5:00 PM

Forum Hall, 4th Floor, Palmer Commons Building

CCMB Seminar Series – joint sponsored by DCMB, Center for RNA Biomedicine, and Department of Human Genetics. 

by Professor Peter Cook, Distinguished Professor of Cell Biology, The Sir William Dunn School of Pathology, University of Oxford

Abstract

I will argue that transcription ‘factories’ are central organizers of the human genome during interphase, and that proximity to an appropriate factory determines the activity of a gene. The nucleolus is the prototypic factory; it is a place where many rRNA genes are efficiently co-transcribed by local concentrations of RNA polymerase I. Analogous clusters of RNA polymerase II in nucleoplasmic factories make protein-coding transcripts. I begin by describing new forces able to drive genome organization uncovered using Brownian dynamic simulations. For example, a diffusion-based “osmotic ratchet” can force bound “slip-links” like cohesin to “convergent” CTCF sites without the need for any motor activity. Additional simulations point to an unforeseen ‘bridging-induced attraction’ that can assemble factories and organize interphase chromosomes at all scales. This organization leads naturally to an explanation of how gene activity is regulated: a promoter is only likely to initiate if tethered near a factory containing appropriate factors. As motifs like enhancers, silencers, insulators, barriers, and boundaries are transcription units, they would work by tethering target promoters close to, or distant from, suitable factories; although we might name the motifs differently, they are all just transcription units influencing promoter-factory distance (and so initiation frequency).