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Isolation and characterization of the human A-myb promoter: regulation by NF-Y and Sp1
- Source :
- Scopus-Elsevier
- Publication Year :
- 2000
-
Abstract
- The A-myb transcription factor shows a restricted tissue distribution and is cell cycle regulated. Furthermore its deregulation has profound effects on the growth and/or differentiation of the cells in which it is normally expressed. We have therefore characterized its promoter. A 12 kb genomic clone was isolated that comprises the first exon, part of the first intron as well as upstream regulatory sequences. Multiple transcription start sites have been identified which operate in both B lymphocytes and epithelial cells and the upsteam region was shown to have promoter, activity. The boundaries of the minimal promoter region (−183−14), of a positive upstream (−538−183) and a negative downstream regulatory region (NRE) (+83+374) have been defined. The NRE is promoter- and orientation-independent but position specific. The A-myb minimal promoter is GC-rich, does not contain any TATA box but has a functional CCAAT box. The CCAAT box and minimal promoter is highly conserved in the corresponding murine sequence. The CCAAT box efficiently binds the NF-Y complex and its mutation decreases basal promoter activity by 50%. Two Sp1 binding sites are present upstream from the CCAAT box which can bind Sp1 and contribute to A-myb promoter activity by 70 and 30%, respectively. The two Sp1 sites and CCAAT box together contribute to over 80% of A-myb basal promoter activity and are therefore the major regulatory elements. Finally, we show that the promoter is cell cycle regulated and that the SP1 and CCAAT elements are required for S phase induction.
- Subjects :
- Cancer Research
Transcription, Genetic
Sp1 Transcription Factor
TATA box
Molecular Sequence Data
CAAT box
Biology
Regulatory Sequences, Nucleic Acid
Cell Line
Exon
Mice
Proto-Oncogene Proteins c-myb
Proto-Oncogene Proteins
Sequence Homology, Nucleic Acid
Genetics
Animals
Humans
MYB
Lymphocytes
Promoter Regions, Genetic
Molecular Biology
Transcription factor
Binding Sites
Base Sequence
Cell Cycle
Intron
Promoter
Molecular biology
DNA-Binding Proteins
Gene Expression Regulation
Regulatory sequence
CCAAT-Enhancer-Binding Proteins
Trans-Activators
Subjects
Details
- ISSN :
- 09509232
- Volume :
- 19
- Issue :
- 34
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....9b039c6540586d52f73b8c9aabdc13a0