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PMID: 8700862 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Expression of the human acute myeloid leukemia gene AML1 is regulated by two promoter regions.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 5 ·1996-03-05 ·Pages 1935-40

Ghozi MC, Bernstein Y, Negreanu V, Levanon D, Groner Y

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.

MeSH Terms
Base Sequence Binding Sites Core Binding Factor Alpha 2 Subunit DNA Primers/chemistry DNA-Binding Proteins Gene Expression Regulation Hematopoiesis Humans Molecular Sequence Data Mutagenesis, Site-Directed Neoplasm Proteins/genetics Promoter Regions, Genetic Proto-Oncogene Proteins Transcription Factors/genetics Transcription, Genetic Tumor Cells, Cultured
Chemicals
Core Binding Factor Alpha 2 Subunit DNA Primers DNA-Binding Proteins Neoplasm Proteins Proto-Oncogene Proteins RUNX1 protein, human Transcription Factors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ghozi M C
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
Bernstein Y
Negreanu V
Levanon D
Groner Y
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.5.1935
Published
1996-03-05
Pages
1935-40
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC39886
Subset
IM
Grants
NICHD NIH HHS · HD21229 · United States
Databases
GENBANK
AF015262, AF025841, AJ229043, U39636, U39637
External Links
PubMed source DOI: 10.1073/pnas.93.5.1935 PMC Full Text View journal details
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