Analysis of mice with single and multiple copies of transgenes reveals a novel arrangement for the lambda 5-V-preB1 locus control region

The murine lambda 5-V-preB1 locus encodes two proteins that form part of th e pre-B-cell receptor and play a key role in B-lymphocyte development. We h ave identified a locus control region (LCR) which is responsible for coordi nate activation of both genes in pre-B cells. Analysis of mice with single and multiple copies of transgenes shows a clear difference in the expressio n behavior of the genes depending on the transgene copy number. While expre ssion of both lambda 5 and V-preB1 in single- and two-copy integrations req uires the presence of a set of DNase I hypersensitive sites located 3' of t he lambda 5 gene, small fragments containing the genes have LCR activity wh en arranged in multiple-copy tandem arrays, indicating that additional comp onents of the LCR are located within or close to the genes. The complete LC R is capable of driving efficient copy-dependent expression of a lambda 5 g ene in pre-B cells even when it is integrated into centomeric gamma-satelli te DNA. The finding that activation of expression of the locus by positivel y acting factors is fully dominant over the silencing effect of heterochrom atin has implications for models for chromatin-mediated gene silencing duri ng B-cell development.