CTCF-Binding Elements Mediate Accessibility of RAG Substrates During Chromatin Scanning

We report that CBEs immediately downstream of frequently rearranged VH-RSSs increase recombination potential of their associated VH far beyond that provided by RSSs alone. This CBE activity becomes particularly striking upon IGCR1 inactivation, which allows RAG, likely via loop extrusion, to linearly scan chromatin far upstream. VH-associated CBEs stabilize interactions of D-proximal VHs first encountered by the DJHRC during linear RAG scanning and thereby promote dominant rearrangement of these VHs by an unanticipated chromatin accessibility-enhancing CBE function. Graphical abstract Teaser RAG endonuclease associated with a DJH recombination center is presented with upstream chromosomal VHs by a linear chromatin scanning process involving loop extrusion. During this process, VH-proximal CTCF looping factor binding elements mediate greatly increased interactions of their associated VHs with the DJH recombination center and, thereby, increase their accessibility for RAG cleavage and subsequent V(D)J recombination.

Source: Cell - May 24, 2018 Category: Cytology Source Type: research