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Expression of the human acute myeloid leukemia gene AML1 is regulated by two promoter regions
- Source :
- Proceedings of the National Academy of Sciences. 93:1935-1940
- Publication Year :
- 1996
- Publisher :
- Proceedings of the National Academy of Sciences, 1996.
-
Abstract
- The human chromosome 21 AML1 gene is expressed predominantly in the hematopoietic system. In several leukemia-associated translocations AML1 is fused to other genes and transcription of the fused regions is mediated by upstream sequences that normally regulate the expression of AML1. The 5' genomic region of AML1 was cloned and sequenced. The two 5' untranslated regions (UTRs) previously identified in AML1 cDNAs were located in this region and the distance between them was established. The distal 5' UTR maps over 7 kb upstream of the proximal one. Using primer extension with mRNA, transcription start sites were identified at two distinct sites above these 5' uTRs. Sequence analysis revealed the absence of a TATA motif and the presence of Sp1, PU.1, Oct, CRE, Myb, Ets, and Ets-like binding sites in both upstream regions. Several initiator elements (Inr) that overlap the transcription start sites were also identified. These proximal and distal upstream regions and their deletion mutants were cloned in front of a luciferase reporter gene and used in transfection assays. We demonstrate that both upstream regions function as promoters in hematopoietic (Jurkat) and nonhematopoietic (HEK) cell lines. The activity of both promoters was orientation dependent and was enhanced, in a cell-type specific manner, by a heterologous enhancer sequence. These results indicate that additional control elements, either negative or positive, regulate the tissue-specific expression of AML1.
- Subjects :
- Untranslated region
Transcription, Genetic
Molecular Sequence Data
Biology
Upstream activating sequence
Transcription (biology)
Proto-Oncogene Proteins
hemic and lymphatic diseases
Tumor Cells, Cultured
Humans
Promoter Regions, Genetic
Enhancer
Gene
Transcription factor
DNA Primers
Regulation of gene expression
Binding Sites
Multidisciplinary
Base Sequence
Promoter
Molecular biology
Hematopoiesis
Neoplasm Proteins
DNA-Binding Proteins
Gene Expression Regulation
Core Binding Factor Alpha 2 Subunit
Mutagenesis, Site-Directed
Research Article
Transcription Factors
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 93
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....2a446bc59f7982cb64bd61b1c608de8e