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PEBP2/CBF, the murine homolog of the human myeloid AML1 and PEBP2 beta/CBF beta proto-oncoproteins, regulates the murine myeloperoxidase and neutrophil elastase genes in immature myeloid cells.
Open accessAbstract
The myeloperoxidase (MPO) and neutrophil elastase genes are expressed specifically in immature myeloid cells. The integrity of a polyomavirus enhancer core sequence, 5'-AACCACA-3', is critical to the activity of the murine MPO proximal enhancer. This element binds two species, myeloid nuclear factors 1 alpha and 1 beta (MyNF1 alpha and -beta), present in 32D cl3 myeloid cell nuclear extracts. The levels of the MyNF1s increase during early 32D cl3 cell granulocytic differentiation. Both MyNF1 alpha and -beta supershift with an antiserum raised by using a peptide derived from the N terminus of polyomavirus enhancer-binding protein 2/core-binding factor (PEBP2/CBF) alpha subunit. The specific peptide inhibits these supershifts. In vitro-translated PEBP2/CBF DNA-binding domain binds the murine MPO PEBP2/CBF site. An alternate PEBP2/CBF consensus site, 5'-GACCGCA-3', but not a simian virus 40 enhancer core sequence, 5'-TTCCACA-3', binds the MyNF1s in vitro and activates a minimal murine MPO-thymidine kinase promoter in vivo. The murine neutrophil elastase gene 100-bp 5'-flanking sequences contain several functional elements, including potential binding sites for PU.1, C/EBP, c-Myb, and PEBP2/CBF. The functional element 5'-GGCCACA-3' located at positions -66 to 72 differs from the PEBP2/CBF consensus (5'-PuACCPuCA-3') only by an A-to-G transition at position 2. This DNA element binds MyNF1 alpha and -beta weakly. The N terminis of two PEBP2/CBF alpha subunit family members, PEBP2 alpha A and PEBP2 alpha B (murine AML1), are nearly identical, and 32D c13 cl3 cells contain both corresponding mRNAs. Since t(8;21), t(3;21), and inv(16), associated with myeloid leukemias, disrupt subunits of PEBP2/CBF, we speculate that the resulting oncoproteins, AML1-ETO, AML1-EAP, AML1-Evi1, and CBF beta-MYH11, inhibit early myeloid differentiation.
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Metadata
- Authors
- Nuchprayoon, I., Meyers, S., Scott, L. M., Suzow, J., Hiebert, S., & Friedman, A. D.
- Affiliations
- Johns Hopkins University (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1994-08
- Volume
- 14
- Issue
- 8
- Pages
- 5558-5568
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC359075
- OpenAlex
- W2124597426
- Cited by
- 296
- References
- 67
- Citations by year
- 2022: 1 · 2021: 4 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 3 · 2013: 6 · 2012: 10
- FWCI
- 8.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Searle Scholars Program
- National Institutes of Health
- National Cancer Institute (R01CA064140, T32CA060441)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- core binding factor, enhancer binding, immature myeloid cells, granulocytic differentiation, myeloid leukemia
- MeSH terms
- Animals, Base Sequence, Binding Sites, Cloning, Molecular, DNA-Binding Proteins, Leukocytes, Molecular Sequence Data, Peroxidase, Neoplasm Proteins, Nuclear Proteins, Oligodeoxyribonucleotides, Pancreatic Elastase, Promoter Regions, Genetic, RNA, Messenger, Transcription Factors, Gene Expression Regulation, Enzymologic, Leukocyte Elastase, Transcription Factor AP-2, Core Binding Factor alpha Subunits, Core Binding Factor beta Subunit, Core Binding Factor Alpha 1 Subunit, Core Binding Factors, Mice, In Vitro Techniques
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