Molecular cloning and characterization of a human DNA binding factor that represses transcription.
Several transcription factors interact with GC-rich sequences and positively regulate both housekeeping genes and cellular oncogenes. We have cloned a human cDNA that encodes a factor that binds to the GC-rich sequences present in the epidermal growth factor receptor (EGFR), beta-actin, and calcium-dependent protease (CANP) promoters. This cDNA encodes a 91 kd protein with an extremely basic region at its amino terminus. Deletion analyses with bacterially expressed proteins containing fragments of this factor indicate that this basic region of the protein functions as the DNA binding domain. Expression of this factor in CV1 cells shows that it represses expression originating from both the EGFR and beta-actin promoters as well as chimeric promoters containing the CANP gene. It also represses transcription in cell-free extracts. These results suggest that positive and negative factors may interact with the same control element to account for the diversity of transcriptional regulation.
Kageyama
R
R
Laboratory of Molecular Biology, National Institutes of Health, Bethesda, Maryland 20892.
Pastan
I
I
D000199:Actins / Q000235:genetics; D000595:Amino Acid Sequence; D001482:Base Composition; D001483:Base Sequence; D002154:Calpain / Q000235:genetics; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000378:metabolism; D003850:Deoxyribonuclease I; D066246:ErbB Receptors / Q000235:genetics; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*
D000199:Actins; D015345:Oligonucleotide Probes; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA; D066246:ErbB Receptors; D003850:Deoxyribonuclease I; D002154:Calpain