A Myc-associated zinc finger protein-related factor binding site is required for the deregulation of c-myc expression by the immunoglobulin heavy chain gene enhancers in Burkitt's lymphoma.
The deregulation of expression of the c-myc gene in Burkitt's lymphoma results from the translocation that links one c-myc allele to one of the immunoglobulin genes. This physical linkage promotes interactions between c-myc and immunoglobulin gene regulatory elements that affect c-myc transcription initiation and elongation. We have located a region in the c-myc promoter that is required for the complete activation by the immunoglobulin heavy chain gene enhancer. This regulatory element contains a core sequence, GGGAGG, similar to the GA box recognized by the transcription factor Myc-associated zinc finger protein (MAZ). UV cross-link analysis indicated that the mass of this protein did not correspond to that of MAZ, suggesting that a protein related to but distinct from MAZ bound to this site. Mutation of this regulatory element resulted in a loss of promoter activity induced by the immunoglobulin heavy chain gene enhancer. This site was also required for the c-myc promoter shift from P2 to P1. In vivo footprinting revealed that this site was occupied on the translocated c-myc allele but not on the untranslocated allele. Taken together, these findings suggest that this regulatory element is required for the full activation of c-myc promoter activity by the immunoglobulin heavy chain gene enhancer.
Hu
Hsien-Ming
HM
Center for Molecular Biology in Medicine, Veterans Affairs Palo Alto Health Care System, Stanford University School of Medicine, Stanford, California 94305, USA.
Arcinas
Magdalena
M
Boxer
Linda M
LM
D000483:Alleles; D001665:Binding Sites; D002051:Burkitt Lymphoma / Q000737:chemistry* / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D004742:Enhancer Elements, Genetic; D017353:Gene Deletion; D005803:Genes, Immunoglobulin / Q000235:genetics*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry*; D008156:Luciferases / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D010957:Plasmids / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection; D014466:Ultraviolet Rays; D016335:Zinc Fingers
D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; C076035:c-MYC-associated zinc finger protein; D008156:Luciferases