Alternative promoters of gene MAGE4a
- Ludwig Inst. for Cancer Research, Brussels (Belgium); and others
Gene MAGE-4 (HGMW-approved symbol MAGE4) is expressed in several types of tumors, but not in normal tissues, except testis and placenta. The 5{prime} end of this gene contains eight homologous exons spread over a 5.8-kb region. These exons are alternatively spliced to a unique second exon and a unique third exon, which encodes a protein of 317 amino acids. The analysis of transcripts found in testis, placenta, and a sarcoma cell line showed that each of the alternative first exons is used in at least one of these tissues. Various regions of the promoter of the fifth alternative exon (1.5) were cloned in a luciferase reporter plasmid, and the constructs were transfected in a sarcoma cell line that expresses MAGE-4. Two Ets motifs located between positions -70 and -29 relative to the transcription start site were found to drive 55% of the promoter activity. A region containing an Sp1 consensus binding site located upstream of the two Ets motifs was found to be responsible for 44% of the transcriptional activity. MAGE-4a promoters 1.4 and 1.6, which also contain the Sp1 and the two Ets binding motifs, supported a level of transcription comparable to that of promoter 1.5, whereas promoter 1.1, which contains only one Ets binding site, was sixfold less active. In line with observations made with gene MAGE-1 (HGMW-approved symbol MAGE1), we found that promoter 1.5 stimulated a high level of transcription in a melanoma cell line that does not express MAGE-4. This suggests that the tumor-specific expression of MAGE genes is not determined by the presence of specific transcription factors. 26 refs., 7 figs., 2 tabs.
- OSTI ID:
- 518478
- Journal Information:
- Genomics, Vol. 40, Issue 2; Other Information: PBD: 1 Mar 1997
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
HUMAN X CHROMOSOME
GENETIC MAPPING
GENES
STRUCTURE-ACTIVITY RELATIONSHIPS
DNA SEQUENCING
GENE REGULATION
SPLICING
TRANSCRIPTION
DNA-CLONING
CARCINOMAS
MELANOMAS
TESTES
GENE REPRESSORS
NEOPLASMS
EXONS
PROTEINS
AMINO ACIDS
TRANSCRIPTION FACTORS
POLYMERASE CHAIN REACTION