To become accessible for rearrangement, the immunoglobulin κ locus must undergo a series of epigenetic changes. This begins in pro-B cells with the relocation of both immunoglobulin κ alleles from the periphery to the center of the nucleus. In pre-B cells, one allele became preferentially packaged into an active chromatin structure characterized by histone acetylation and methylation of histone H3 lysine 4, while the other allele was recruited to heterochromatin, where it was associated with heterochromatin protein-γ and Ikaros. These events in cis made only one allele accessible to trans-acting factors, such as RelB, which mediated DNA demethylation, to facilitate rearrangement. These results suggest that early B lymphoid epigenetic changes generate differential structures that serve as the basis for allelic exclusion.
Bibliographical noteFunding Information:
We thank T. Wirth (Ulm University, Ulm, Germany) for the RelB expression plasmid, and L. Lande for help in completing this project. Supported by the Israel Academy of Sciences (H.C. and Y.B.), NIH (H.C. and Y.B.), Israel Cancer Research Foundation (H.C.), European Community 5th Framework Quality of Life Program (Y.B.), Wellcome Trust University Award (J.S.) and a Horvitz Fellowship (M.G.).