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PMID: 9632776 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Multiple functional domains of AML1: PU.1 and C/EBPalpha synergize with different regions of AML1.

Molecular and cellular biology ·Vol. 18 ·No. 7 ·1998-07-00 ·Pages 3915-25

Petrovick MS, Hiebert SW, Friedman AD, Hetherington CJ, Tenen DG, Zhang DE

Abstract

Control elements of many genes are regulated by multiple activators working in concert to confer the maximal level of expression, but the mechanism of such synergy is not completely understood. The promoter of the human macrophage colony-stimulating factor (M-CSF) receptor presents an excellent model with which we can study synergistic, tissue-specific activation for two reasons. First, myeloid-specific expression of the M-CSF receptor is regulated transcriptionally by three factors which are crucial for normal hematopoiesis: PU.1, AML1, and C/EBPalpha. Second, these proteins interact in such a way as to demonstrate at least two examples of synergistic activation. We have shown that AML1 and C/EBPalpha activate the M-CSF receptor promoter in a synergistic manner. As we report here, AML1 also synergizes, and interacts physically, with PU. 1. Detailed analysis of the physical and functional interaction of AML1 with PU.1 and C/EBPalpha has revealed that the proteins contact one another through their DNA-binding domains and that AML1 exhibits cooperative DNA binding with C/EBPalpha but not with PU.1. This difference in DNA-binding abilities may explain, in part, the differences observed in synergistic activation. Furthermore, the activation domains of all three factors are required for synergistic activation, and the region of AML1 required for synergy with PU.1 is distinct from that required for synergy with C/EBPalpha. These observations present the possibility that synergistic activation is mediated by secondary proteins contacted through the activation domains of AML1, C/EBPalpha, and PU.1.

MeSH Terms
Animals Binding Sites CCAAT-Enhancer-Binding Proteins COS Cells Cell Line Chlorocebus aethiops Core Binding Factor Alpha 2 Subunit DNA/metabolism DNA-Binding Proteins/metabolism HeLa Cells Humans Mutagenesis Nuclear Proteins/metabolism Phosphorylation Promoter Regions, Genetic Proto-Oncogene Proteins/metabolism Receptor, Macrophage Colony-Stimulating Factor/genetics Trans-Activators/metabolism Transcription Factors/metabolism Transcriptional Activation
Chemicals
CCAAT-Enhancer-Binding Proteins Core Binding Factor Alpha 2 Subunit DNA-Binding Proteins Nuclear Proteins Proto-Oncogene Proteins RUNX1 protein, human Trans-Activators Transcription Factors proto-oncogene protein Spi-1 DNA Receptor, Macrophage Colony-Stimulating Factor
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Petrovick M S
Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Hiebert S W
Friedman A D
Hetherington C J
Tenen D G
Zhang D E
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.7.3915
Published
1998-07-00
Pages
3915-25
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC108976
Subset
IM
Grants
NCI NIH HHS · CA/AI59589 · United States
NCI NIH HHS · CA72009 · United States
NCI NIH HHS · CA41456 · United States
External Links
PubMed source DOI: 10.1128/MCB.18.7.3915 PMC Full Text View journal details
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