Combinatorial regulation of the murine RAG-2 promoter by Sp1 and distinct lymphocyte-specific transcription factors

Authors

Gustavo A. Miranda, University of California, Los Angeles
Maria Villalvazo, University of California, Los Angeles
Zoran Galic, University of California, Los Angeles
Jackelyn Alva, University of California, Los Angeles
Roxanna Abrines, University of California, Los Angeles
Yvette Yates, University of California, Los Angeles
Cory J. Evans, University of California, Los AngelesFollow
Renato J. Aguilera, University of California, Los Angeles

Document Type

Article

Publication Date

2002

Abstract

The recombination activation genes, RAG-1 and RAG-2, encode the critical components of the recombinase complex responsible for the generation of functional antigen receptor genes. In order to gain an insight into the transcription factors and cis-acting elements that regulate the lymphocyte-specific expression of RAG-2, the promoter-region of this gene was isolated and characterized. This analysis demonstrated that a relatively small promoter fragment could confer lymphocyte-restricted expression to a reporter construct. Our work and that of others subsequently revealed that RAG-2 promoter expression is positively regulated by BSAP (PAX-5) and c-Myb transcription factors in B- and T-lineage cells, respectively. Although BSAP and c-Myb were deemed necessary for lymphocyte-specific expression, our analysis also uncovered a G-rich region at the 5′-end of the core promoter that was essential for full activity in lymphocyte cell lines. Site-directed mutagenesis revealed that a GA-box within the G-rich region was required for full promoter activity and subsequent DNA binding assays demonstrated that this element was specifically recognized by Sp1. Apart from showing that Sp1 interacts within the RAG-2 promoter, we also demonstrate that the Sp1-binding site is necessary for the high-level activation of this promoter.

Comments

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Original Publication Citation

Miranda, Gustavo A., et al. “Combinatorial Regulation of the Murine RAG-2 Promoter by Sp1 and Distinct Lymphocyte-Specific Transcription Factors.” Molecular Immunology, vol. 38, no. 15, Jan. 2002, pp. 1151–1159. DOI: 10.1016/S0161-5890(02)00007-X

Digital Commons @ LMU & LLS Citation

Miranda, Gustavo A.; Villalvazo, Maria; Galic, Zoran; Alva, Jackelyn; Abrines, Roxanna; Yates, Yvette; Evans, Cory J.; and Aguilera, Renato J., "Combinatorial regulation of the murine RAG-2 promoter by Sp1 and distinct lymphocyte-specific transcription factors" (2002). Biology Faculty Works. 132.
https://digitalcommons.lmu.edu/bio_fac/132