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 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.
Brys
A
A
Department of Molecular Biophysics and Biochemistry, Yale Medical School, New Haven, CT 06510.
Maizels
N
N
D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003850:Deoxyribonuclease I; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D004268:DNA-Binding Proteins; C484201:LR1 protein, human; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D003850:Deoxyribonuclease I