Dr. Aafke van den Berg
Post-Doctoral Fellow, Massachusetts Institute of Technology (MIT), Institute for Medical Engineering and Science
Lab Website (Dr. Leonid Mirny)
Transcription shapes 3D organization of mammalian chromatin
Thursday, September 12, 2019
2 PM
RRI 101
Abstract: Recent theoretical and experimental studies indicate that the process of loop extrusion is one of the main mechanisms underlying chromosome organization during interphase. According to the model for loop extrusion, a cohesin complex is loaded onto chromatin and extrudes loops until it dissociates or encounters an obstacle such as CTCF. We aim to understand what genomic elements other than CTCF sites, and what processes on DNA can act as extrusion barriers, thus shaping chromosome organization.
We analyzed data from new experiments that remove CTCF and extend cohesin residence time and found profound changes of chromosome folding near active genes. To explain these changes we propose the moving barrier model where cohesin cannot bypass an elongating PolII. As a result cohesin traces PolII at its low speed in the direction of transcription, while a cohesin approaching PolII in the opposite direction is shoveled back to the end of the gene.
The moving barrier model recapitulates both ChIP-seq patterns of cohesin accumulation and patterns in Hi-C around active genes. Interestingly, the model also provides a long-sought mechanism for dynamic enhancer-PolII tracking during transcription elongation. I will discuss how future in vitro and time course experiments can further test the moving barrier model.
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