LR1 Regulates c-Myc Transcription in B-Cell Lymphomas

LR1 is a 106-kDa sequence-specific DNA-binding protein first identified as a potential regulator of immunoglobulin class switch recombination in B lymphocytes. Here we report that LR1 binds to a site 310 nt upstream of the human c-myc P1 promoter. Mutation of this site decreases reporter gene expres...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1994-05, Vol.91 (11), p.4915-4919
Main Authors: Brys, April, Maizels, Nancy
Format: Article
Language:English
Subjects:
B cell lymphoma
B lymphocytes
Base Sequence
Binding Sites
Biochemistry
Deoxyribonuclease I
Deoxyribonucleic acid
DNA
DNA Primers
DNA-Binding Proteins - metabolism
Gels
Gene Expression Regulation, Neoplastic
Genes, myc
Genetic loci
Genetic mutation
Humans
Lymphoma, B-Cell - genetics
Molecular Sequence Data
Oligonucleotides
Promoter regions
Promoter Regions, Genetic
Proteins
Proto-Oncogene Proteins c-myc - genetics
Transcription Factors - metabolism
Transcription, Genetic
Transfection
Tumor Cells, Cultured
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Description
Summary:LR1 is a 106-kDa sequence-specific DNA-binding protein first identified as a potential regulator of immunoglobulin class switch recombination in B lymphocytes. Here we report that LR1 binds to a site 310 nt upstream of the human c-myc P1 promoter. Mutation of this site decreases reporter gene expression 5.5-fold in the Burkitt lymphoma line Raji and 3.8-fold in the lymphoma line BJAB. These experiments show that LR1 can function as a transcription factor and identify it as a cell type-specific activator of c-myc expression. There are multiple matches to the LR1 recognition consensus at the immunoglobulin heavy-chain locus and at c-myc, which further suggests that LR1 may play a dual role, facilitating c-myc translocation as well as regulating c-myc transcription.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.91.11.4915