Mapping and functional analysis of regulatory sequences in the mouse lambda5-VpreB1 domain.
The lambda5 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 lambda5 and VpreB1 genes are closely linked and are co-regulated by a multi-component locus control region. To identify the sequences that regulate lambda5 and VpreB1 expression during B cell development, we have comprehensively mapped the DNaseI hypersensitive sites (HS) in the lambda5-VpreB1 functional domain. The active domain contains 12 HS that are distributed at high density across the 18.3 kb region that forms the lambda5 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 lambda5. The lambda5-VpreB1 locus was also found to be closely linked to the ubiquitously expressed Topoisomerase-3beta (Topo3beta) gene. The VpreB1 and Topo3beta genes have entirely different expression patterns despite the fact that the two promoters are separated by a distance of only 1.5 kb.
Minaee
Sophia
S
Gene regulation and Chromatin Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 ONN, UK.
Farmer
Deborah
D
Georgiou
Andrew
A
Sabbattini
Pierangela
P
Webster
Zoe
Z
Chow
Cheok-Man
CM
Dillon
Niall
N
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D003850:Deoxyribonuclease I; D004742:Enhancer Elements, Genetic; D005809:Genes, Regulator; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D054444:Immunoglobulin Light Chains, Surrogate; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D010957:Plasmids / Q000235:genetics; D054420:Pre-B Cell Receptors; D011401:Promoter Regions, Genetic; D011947:Receptors, Antigen, B-Cell
D018076:DNA, Complementary; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007135:Immunoglobulin Variable Region; D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D003850:Deoxyribonuclease I