Mapping and functional analysis of regulatory sequences in the mouse λ5-VpreB1 domain

The λ5 and VpreB genes encode the components of the surrogate light-chain which forms part of the pre-B cell receptor and plays a key role in B cell development. In the mouse, the λ5 and VpreB1 genes are closely linked and are co-regulated by a multi-component locus control region. To identify the sequences that regulate λ5 and VpreB1 expression during B cell development, we have comprehensively mapped the DNaseI hypersensitive sites (HS) in the λ5-VpreB1 functional domain. The active domain contains 12 HS that are distributed at high density across the 18.3 kb region that forms the λ5 and VpreB1 functional unit. Analysis of a reporter gene driven by the VpreB1 promoter in transgenic mice identified a novel enhancer associated with two HS located upstream of λ5. The λ5-VpreB1 locus was also found to be closely linked to the ubiquitously expressed Topoisomerase-3β (Topo3β) gene. The VpreB1 and Topo3β genes have entirely different expression patterns despite the fact that the two promoters are separated by a distance of only 1.5 kb.