Cited by 296Genomics and Chromatin DynamicsAcute Myeloid Leukemia ResearchRetinoids in leukemia and cellular processes

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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.

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Nuchprayoon, I, Meyers, S, Scott, L M, Suzow, J, Hiebert, S, Friedman, A D·1994·Molecular and Cellular Biology

DOI 10.1128/mcb.14.8.5558PMC PMC359075

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Abstract

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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Authors: Nuchprayoon, I., Meyers, S., Scott, L. M., Suzow, J., Hiebert, S., & Friedman, A. D.
Affiliations: Johns Hopkins University (US)
ORCID: Nuchprayoon, I
Hiebert, S
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
DOI: 10.1128/mcb.14.8.5558
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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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.

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