Fred Alt - The Fundamental Mechanistic Roles of Chromatin Loop Extrusion in Antibody Gene ...

Professor Alt described the mechanism of cohesin-mediated chromatin loop extrusion in antibody gene diversification. In pro-B cells, RAG endonuclease mediates recombination of V, D and J fragments to form variable region exons in the Igh locus. During IgH rearrangements, cohesin is anchored at the recombination center and extrudes DNA through the cohesin ring, allowing the D and VH segments to enter the recombination center where the RAG enzyme mediates rearrangement of D-to-JH first and then VH-to-DJH. During Igκ light chain rearrangement in pre-B cells, loop extrusion also brings Vκ and Jκ segments close to each other, but it was predominantly the strong recombination signal sequences (RSSs) associated with Vκs and Jκs that mediates diffusional rearrangement. This study enriched the knowledge of epigenetics in antibody rearrangement.