Control of V(D)J Recombination through Transcriptional Elongation and Changes in Locus Chromatin Structure and Nuclear Organization

Figure 4

Representation of the molecular mechanism for activation of V(D)J recombination by enhancers, promoters, and transcription. Shown is a depiction of the physical interaction between the enhancer and the promoter within an antigen receptor locus. This interaction is mediated through protein-protein interactions among transcription factors and triggers the processes of transcription and V(D)J recombination that is derived from chromatin opening and subsequent accessibility of the RSSs to the RNAPII and RAG-1/2 proteins. Gene segments are represented as red and green rectangles and RSSs as white triangles. (a) Enhancer activation by the assembly of a functional multiprotein complex on the enhancer mediates the recruitment of the RNAPII to the promoter. This activates germline transcription (blue arrow) and opens the chromatin structure by repositioning nucleosomes, evicting nucleosomes, and/or changing the covalent modifications of histones (e.g., changing H3K9me, which is indicative of repressive chromatin, to H3K4me and H3/H4ac, which are indicative of activated chromatin). (b) The new chromatin configuration allows recruitment of the RAG-2 protein through H3K4me3 and recruitment of the RAG-1 protein to accessible RSSs. Recruitment of a RAG-1/2 complex to two compatible RSSs allows initiation of V(D)J recombination.