How do Cohesin and CTCF Fold DNA in Mammalian Genomes?

Talk Overview

It has been known for many years that the protein cohesin is necessary to join sister chromatids together before they are segregated during mitosis.  Electron micrographs have shown that cohesin subunits form a ring complex which is thought to encircle the DNA keeping the chromatids together. When they need to separate during anaphase, the cohesin complex is removed by another set of proteins.  In his first talk, Dr. Peters explains how observations that he and others made suggested that cohesin may have additional roles in the cell. For instance, cohesin is initially loaded onto chromosome arms at discrete sites and in much larger amounts than is needed for chromatid cohesion. Cohesin also was shown to co-localize on chromosomes with a DNA binding protein called CTCF. CTCF is known to regulate transcription by forming DNA loops.  Peters explains that, taken together, these observations hinted at a role for cohesin and CTCF in folding DNA into loops to allow efficient packing of very large eukaryotic genomes into small cell nuclei, and regulating functions such as gene expression.

In his second talk, Peters presents evidence that cohesin is indeed necessary for genomic DNA to fold into loops. Long range DNA interactions such as loops can be detected using a technique called Hi-C. Using Hi-C, Peters shows that depleting cohesin removes DNA loops, while depleting the proteins that remove cohesin from DNA, results in bigger DNA loops. In addition, CTCF appears to recognize specific sequences that define the base of the loops.  Incorporating all of this data, Peters describes a model in which DNA is extruded by cohesin to form a loop and the boundaries of the loop are determined by CTCF. Peters explains that many questions about the mechanism of DNA loop extrusion and its importance in cells remain to be answered.

Speaker Bio

Jan-Michael Peters

Dr. Jan-Michael Peters earned his Diploma in biology and his PhD in cell biology from the University of Heidelberg.  He did a short post-doc with Werner Franke at the German Cancer Research Center (DKFZ), before moving to the Harvard School of Medicine to continue his training with Marc Kirschner.  Peters returned to Europe in 1996… Continue Reading