Inhibition of hematopoiesis by competitive binding of transcription factor PU.1
Open accessAbstract
Transcription factors have been shown to play a role as "master switch" factors in the programming of hematopoietic cell commitment and differentiation. PU.1 is a hematopoietic-specific member of the Ets family of transcription factors. In human bone marrow CD34-enriched progenitor cells, PU.1 expression was upregulated during the early phases of granulocytic/monocytic differentiation, preceding expression of its target genes encoding CD11b and the macrophage-colony-stimulating factor receptor, whereas PU.1 was expressed at stable levels throughout erythroid differentiation. To study PU.1 function, we synthesized double-stranded phosphorothioate oligonucleotides containing a characterized PU.1 site and demonstrated their ability to specifically compete for PU.1 DNA binding. When added to CD34+ cells in vitro, wild-type PU.1-binding oligonucleotides significantly blocked hematopoietic colony formation, whereas mutated PU.1 oligonucleotides which no longer bind PU.1 had no specific inhibitory effect. These results demonstrate that PU.1 is developmentally upregulated during normal human myelopoiesis and that the function of PU.1 is critical for the development of in vitro hematopoiesis.
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- Authors
- Voso, M. T., Burn, T. C., Wulf, G., Lim, B., Leone, G., & Tenen, D. G.
- Affiliations
- Harvard University (US)
- Università Cattolica del Sacro Cuore (IT)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1994-08-16
- Volume
- 91
- Issue
- 17
- Pages
- 7932-7936
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC44518
- OpenAlex
- W2026663073
- Cited by
- 141
- References
- 37
- Citations by year
- 2023: 1 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 1
- FWCI
- 7.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Funders
- Brigham and Women's Hospital
- National Institutes of Health (5p01ca034183-11, 5r29dk044099-05)
- National Cancer Institute (CA 41456, R01CA041456, CA 34183)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK44099)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- PU.1, ETS transcription factors, hematopoiesis, myelopoiesis, phosphorothioate oligonucleotides, CD34+ cells, hematopoietic colony formation, granulocytic differentiation, monocyte differentiation, erythroid differentiation, CD11b, macrophage colony-stimulating factor receptor
- MeSH terms
- Base Sequence, Binding, Competitive, Bone Marrow Cells, Cells, Cultured, Colony-Forming Units Assay, DNA-Binding Proteins, Hematopoiesis, Hematopoietic Stem Cells, Humans, Molecular Sequence Data, Oligodeoxyribonucleotides, RNA, Messenger, Thionucleotides, Transcription Factors, Retroviridae Proteins, Oncogenic, Antigens, CD, Gene Expression, Macrophage Colony-Stimulating Factor, Receptor, Macrophage Colony-Stimulating Factor, Mutagenesis, CD11 Antigens, Antigens, CD34, Erythroid-Specific DNA-Binding Factors
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