A region of the 20 bp repeats lies 3' of human Ig Calpha1 and Calpha2 genes

Abstract

The murine Ig heavy chain gene locus is regulated by multiple elements. In addition to the intron enhancer, Emu, there is a complex regulatory region 3' of the Calpha gene, which spans approximately 40 kb and contains several enhancers. In contrast to mouse, the human IgH cluster contains two Calpha genes, each associated with duplicated arrays of other CH genes. There is evidence to suggest that each array is individually regulated. In this report, we describe an approximately 2 kb region containing 20 bp repeats that lies 3' of both human Calpha1 and Calpha2 genes. This repeat region appears to be the site of integration of the Epstein-Barr virus in the RGN1 B lymphoma cell line. The repeat region is homologous to a 420 bp segment in mouse that is located downstream of the Calpha membrane exon in the interval preceding the second of three poly(A) termination sites. However, in contrast to human, the murine segment contains degenerate repeats. The human repeat region bears significant homology to switch sequences, in particular to Smu and Salpha. We hypothesize that the human repeat regions may play a role in the class switch process by contributing to the stabilization of interactions between the two switch regions. The presence of a Sau3A site within the repeats presents a barrier to cloning with several existing human genomic libraries, most of which are based on partial Sau3A digestion. Furthermore, the homology of the repeat region with Smu and Salpha sequences may contribute to the difficulty in isolating YAC clones containing Calpha genes since homologous recombination could potentially have deleted this entire segment. Our map of these DNA segments provides a guide to their isolation and characterization.