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PMID: 8264604 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Molecular and cellular biology ·Vol. 14 ·No. 1 ·1994-01-00 ·Pages 373-81

Zhang DE, Hetherington CJ, Chen HM, Tenen DG

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.

MeSH Terms
Amino Acid Sequence B-Lymphocytes/metabolism Base Sequence Binding Sites/genetics Cell Line DNA/genetics DNA-Binding Proteins/metabolism Gene Expression Regulation Humans Macrophages/metabolism Molecular Sequence Data Monocytes/metabolism Mutagenesis, Site-Directed Promoter Regions, Genetic Receptor, Macrophage Colony-Stimulating Factor/genetics Retroviridae Proteins, Oncogenic Tissue Distribution Transcription Factors/metabolism Transcription, Genetic
Chemicals
DNA-Binding Proteins Retroviridae Proteins, Oncogenic Transcription Factors v-Spi-1 protein, Friend spleen focus-forming virus DNA Receptor, Macrophage Colony-Stimulating Factor
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Zhang D E
Department of Medicine, Beth Israel Hospital, Boston, Massachusetts 02115.
Hetherington C J
Chen H M
Tenen D G
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.14.1.373-381.1994
Published
1994-01-00
Pages
373-81
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC358386
Subset
IM
Grants
NCI NIH HHS · CA41456 · United States
External Links
PubMed source DOI: 10.1128/mcb.14.1.373-381.1994 PMC Full Text View journal details
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