A region of 20 bp repeats lies 3′ of human Ig C_α1 and C_α2 genes

The murine Ig heavy chain gene locus is regulated by multiple elements. In addition to the intron enhancer, E_μ, there is a complex regulatory region 3′ of the C_α gene, which spans ∼40 kb and contains several enhancers. In contrast to mouse, the human IgH cluster contains two C_α genes, each associated with duplicated arrays of other C_H genes. There is evidence to suggest that each array is individually regulated. In this report, we describe an ∼2 kb region containing 20 bp repeats that lies 3′ of both human C_α1 and C_α2 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 C_α 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 S_μ and S_α. 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 S_μ and S_α sequences may contribute to the difficulty in isolating YAC clones containing C_α, 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.