A novel enhancer in the immunoglobulin lambda locus is duplicated and functionally independent of NF kappa B.
Open accessAbstract
As a first step toward defining the elements necessary for lambda immunoglobulin gene regulation, DNase I hypersensitive sites were mapped in the mouse lambda locus. A hypersensitive site found 15.5 kb downstream of C lambda 4 was present in all the B-cell but not in the T-cell lines tested. This site coincided with a strong B-cell-specific transcriptional enhancer (E lambda 2-4). This novel enhancer is active in myeloma cells, regardless of the status of endogenous lambda genes, but is inactive in a T-cell line and in fibroblasts. The enhancer E lambda 2-4 functions in the absence of the transcription factor NF kappa B, which is necessary for kappa enhancer function. No evidence could be found for NF kappa B binding by this element. Rearrangement of V lambda 2 to JC lambda 3 or JC lambda genes deletes E lambda 2-4; however, a second strong enhancer was found 35 kb downstream of C lambda 1, which cannot be eliminated by lambda gene rearrangements. The second lambda enhancer (E lambda 3-1) is 90% homologous to the E lambda 2-4 sequence in the region determined to comprise the active enhancer and likewise lacks the consensus binding site for NF kappa B. The data support a model for the independent activation of kappa and lambda gene expression based on locus-specific regulation at the enhancer level.
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Each enhancer contains an essential composite site (λB) bound by PU.1 and Pip.
“Each enhancer contains an essential composite site (λB) bound by PU.1 and Pip”
From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Hagman et al., 1990
The Abstract identifies two lambda enhancers, and “Cloning of a second enhancer and comparison with” discusses conserved sequence motifs. Neither passage identifies an essential λB composite site or reports binding by PU.1 and Pip; searches for those terms found no supporting passage in our copy. (LLM, conf=0.76)
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References 82 · Cited by 100
Research works printed but not linked: 2
- Hagman, J. 1989. Murine immunoglobulin lambda genes are regulated by downstream enhancer elements. Ph.D. thesis. University of Washington, Seattle.
- Miller, J. 1983. The mouse immunoglobulin k light chain gene family. Ph.D. thesis, University of Washington, Seattle.
- Authors
- Hagman, J., Rudin, C. M., Haasch, D., Chaplin, D., & Storb, U.
- Affiliations
- University of Chicago (US)
- Washington University in St. Louis (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1990-06
- Volume
- 4
- Issue
- 6
- Pages
- 978-992
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2040720915
- Cited by
- 100
- References
- 82
- Citations by year
- 2023: 3 · 2022: 2 · 2021: 1 · 2020: 1 · 2014: 2 · 2013: 2
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Arthritis Foundation
- National Institutes of Health (2r01gm038649-10a1)
- National Institute of General Medical Sciences (T32GM007281, GM-07281, GM-38649)
- National Institute of Allergy and Infectious Diseases (AI-24780)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- enhancers, DNase I hypersensitive sites, myeloma cells
- MeSH terms
- Animals, B-Lymphocytes, Base Sequence, Binding, Competitive, Cell Line, Cloning, Molecular, Cosmids, Deoxyribonuclease I, DNA-Binding Proteins, Enhancer Elements, Genetic, Fibroblasts, Gene Expression Regulation, Genes, Immunoglobulin, Immunoglobulin lambda-Chains, Molecular Sequence Data, T-Lymphocytes, Transcription Factors, Tumor Cells, Cultured, Restriction Mapping, NF-kappa B
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