Cited by 411Genomics and Chromatin DynamicsImmune cells in cancerCytokine Signaling Pathways and Interactions

The macrophage transcription factor PU.1 directs tissue-specific expression of the macrophage colony-stimulating factor receptor

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Zhang, Dong-Er, Hetherington, Christopher J., Chen, Hui-Min, Tenen, Daniel G.·1994·Molecular and Cellular Biology

Abstract

The macrophage colony-stimulating factor (M-CSF) receptor is expressed in a tissue-specific fashion from two distinct promoters in monocytes/macrophages and the placenta. In order to further understand the transcription factors which play a role in the commitment of multipotential progenitors to the monocyte/macrophage lineage, we have initiated an investigation of the factors which activate the M-CSF receptor very early during the monocyte differentiation process. Here we demonstrate that the human monocytic M-CSF receptor promoter directs reporter gene activity in a tissue-specific fashion. Since one of the few transcription factors which have been implicated in the regulation of monocyte genes is the macrophage- and B-cell-specific PU.1 transcription factor, we investigated whether PU.1 binds and activates the M-CSF receptor promoter. Here we demonstrate that both in vitro-translated PU.1 and PU.1 from nuclear extracts bind to a specific site in the M-CSF receptor promoter just upstream from the major transcription initiation site. Mutations in this site which eliminate PU.1 binding decrease M-CSF receptor promoter activity significantly in macrophage cell lines only. Furthermore, PU.1 transactivates the M-CSF receptor promoter in nonmacrophage cells. These results suggest that PU.1 plays a major role in macrophage gene regulation and development by directing the expression of a receptor for a key macrophage growth factor.

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Crossref · 10.1128/mcb.14.1.373-381.1994

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Authors
Zhang, D.-E., Hetherington, C. J., Chen, H.-M., & Tenen, D. G.
Affiliations
Beth Israel Deaconess Medical Center (US)
Venue
Molecular and Cellular Biology
Published
1994-01
Volume
14
Issue
1
Pages
373-381
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
OpenAlex
W2122968144
Cited by
411
References
47
Citations by year
2026: 3 · 2025: 8 · 2024: 4 · 2023: 7 · 2022: 11 · 2021: 9 · 2020: 10 · 2019: 5 · 2018: 10 · 2017: 7 · 2016: 8 · 2015: 12 · 2014: 10 · 2013: 13 · 2012: 5
FWCI
11.28
Type
journal article
Language
en
Open access
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (CA 41456, R01CA041456)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
PU.1, macrophage colony-stimulating factor receptor, transcription factor binding sites, promoter transactivation, tissue-specific gene expression, monocyte differentiation, placenta, monocytic cells, transcriptional regulation
MeSH terms
Amino Acid Sequence, B-Lymphocytes, Base Sequence, Binding Sites, Cell Line, DNA, DNA-Binding Proteins, Gene Expression Regulation, Humans, Macrophages, Molecular Sequence Data, Monocytes, Promoter Regions, Genetic, Tissue Distribution, Transcription Factors, Transcription, Genetic, Retroviridae Proteins, Oncogenic, Receptor, Macrophage Colony-Stimulating Factor, Mutagenesis, Site-Directed

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