The DOI matches its Crossref record; 44 of the 46 references it cites were found in a registry or an index.
GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription
Abstract
The GATA-1 transcription factor is capable of suppressing the myeloid gene expression program when ectopically expressed in myeloid cells. We examined the ability of GATA-1 to repress the expression and function of the PU.1 transcription factor, a central regulator of myeloid differentiation. We found that GATA-1 is capable of suppressing the myeloid phenotype without interfering with PU.1 gene expression, but instead was capable of inhibiting the activity of the PU.1 protein in a dose-dependent manner. This inhibition was independent of the ability of GATA-1 to bind DNA, suggesting that it is mediated by protein-protein interaction. We examined the ability of PU.1 to interact with GATA-1 and found a direct interaction between the PU.1 ETS domain and the C-terminal finger region of GATA-1. Replacing the PU.1 ETS domain with the GAL4 DNA-binding domain removed the ability of GATA-1 to inhibit PU.1 activity, indicating that the PU.1 DNA-binding domain, rather than the transactivation domain, is the target for GATA-1–mediated repression. We therefore propose that GATA-1 represses myeloid gene expression, at least in part, through its ability to directly interact with the PU.1 ETS domain and thereby interfere with PU.1 function.
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In the citing paper
“suggesting that GATA-1 can directly inhibit PU.1 activity (54; see below).”
From Inhibition of CBP-Mediated Protein Acetylation by the Ets Family Oncoprotein PU.1 (2002) · cites this paper as [54]
In the citing paper
“with GATA-1 repressing PU.1 activity during erythropoiesis”
From Molecular Analysis of the Interaction between the Hematopoietic Master Transcription Factors GATA-1 and PU.1 (2006) · cites this paper as [13]
In the citing paper
“PU.1 repressing GATA-1 function during myelopoiesis”
From Molecular Analysis of the Interaction between the Hematopoietic Master Transcription Factors GATA-1 and PU.1 (2006) · cites this paper as [13]
In the citing paper
“It has also been shown in several independent studies that the two proteins are able to physically interact both in vitro and in a cellular context.”
From Molecular Analysis of the Interaction between the Hematopoietic Master Transcription Factors GATA-1 and PU.1 (2006) · cites this paper as [13]
In the citing paper
“Taken together, these data appear to indicate that a direct interaction can take place between GATA-1 and PU.1”
From Molecular Analysis of the Interaction between the Hematopoietic Master Transcription Factors GATA-1 and PU.1 (2006) · cites this paper as [13]
In the citing paper
“the regions responsible for this interaction are the C-terminal zinc finger of GATA-1 (CF) and the Ets domain of PU.1”
From Molecular Analysis of the Interaction between the Hematopoietic Master Transcription Factors GATA-1 and PU.1 (2006) · cites this paper as [13]
In the citing paper
“yet the two cysteine mutations failed to disrupt either the interaction with PU.1 or the ability of GATA-1 to inhibit transactivation by PU.1”
From Molecular Analysis of the Interaction between the Hematopoietic Master Transcription Factors GATA-1 and PU.1 (2006) · cites this paper as [13]
In the citing paper
“this result was surprising at the time, but can be explained by the data obtained in our study, because the CFtail region remained intact and our results indicate that it is this region that makes a major contribution to the binding to PU.1-Ets.”
From Molecular Analysis of the Interaction between the Hematopoietic Master Transcription Factors GATA-1 and PU.1 (2006) · cites this paper as [13]
In the citing paper
“The evolutionarily conserved DNA binding domain (also known as ETS domain) is confined to the C-terminus of PU.1 and mediates its binding to DNA as well as interaction with a number of other proteins such as c-Jun, GATA-1, GATA-2, C/EBP-α and -β and AML-1[40–42].”
From PU.1 and partners: regulation of haematopoietic stem cell fate in normal and malignant haematopoiesis (2009) · cites this paper as [42]
In the citing paper
“Several lines of evidence suggest that GATA-1 and PU.1 functionally antagonize each other through direct physical interaction via the DNA-binding domains of both proteins [41, 42, 65].”
From PU.1 and partners: regulation of haematopoietic stem cell fate in normal and malignant haematopoiesis (2009) · cites this paper as [42]
In the citing paper
“Of interest is that PU.1 and GATA-1 both potentially exhibit autoregulation”
From Potential Autoregulation of Transcription Factor PU.1 by an Upstream Regulatory Element (2005) · cites this paper as [38]
In the citing paper
“whereas at the same time interactions between these two mediate inhibition of each other's function (38,52,66,67).”
From Potential Autoregulation of Transcription Factor PU.1 by an Upstream Regulatory Element (2005) · cites this paper as [38]
In the citing paper
“and shown that failure to downregulate PU.1 would result in inhibition of the essential erythroid regulator GATA-1 (38,52,66,67).”
From Potential Autoregulation of Transcription Factor PU.1 by an Upstream Regulatory Element (2005) · cites this paper as [38]
In the citing paper
“GATA-1 and the ets factor PU.1 have been reported to functionally antagonize one another in the regulation of erythroid versus myeloid gene transcription and development.”
From Novel Combinatorial Interactions of GATA-1, PU.1, and C/EBPε Isoforms Regulate Transcription of the Gene Encoding Eosinophil Granule Major Basic Protein (2002) · cites this paper as [12]
In the citing paper
“may serve to either up-regulate or down-regulate eosinophil gene transcription through synergistic or antagonistic interactions with GATA-1, dependent upon its expression level relative to GATA-1 (3,12).”
From Novel Combinatorial Interactions of GATA-1, PU.1, and C/EBPε Isoforms Regulate Transcription of the Gene Encoding Eosinophil Granule Major Basic Protein (2002) · cites this paper as [12]
In the citing paper
“A similar phenomenon is observed with the transcription factor GATA1, which interacts with PU.1 and represses PU.1-dependent transactivation capacity.1,36”
From Granulocyte inducer C/EBPα inactivates the myeloid master regulator PU.1: possible role in lineage commitment decisions (2002) · cites this paper as [1]
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Does C-Myb Have A Role In Haemopoietic Stem Cells And Multilineage Progenitors?
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“1 and GATA-1 is a major determinant of erythroid versus myelomonocytic differentiation (Rekhtman et al., 1999; Nerlov et al., 2000).”
BackgroundAvian Lymphopoiesis and Transcriptional Control of Hematopoietic Stem Cell Differentiation
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Globin Gene Expression: Role of Transcription Factors
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FUNCTIONAL AND MECHANISTIC STUDY OF DOT1L IN MOUSE EMBRYONIC HEMATOPOIESIS
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Transcription Regulation in B-cell Development
Ishii, H., Chowdhury, D., & Sen, R. (2004) · Elsevier eBooks · doi:10.1016/b978-012436643-5/50098-5
THE BIOLOGICAL FUNCTION OF INTERACTING PARTNERS OF ZXD FAMILY PROTEINS
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“For both, GATA-1 and PU.1, it has been demonstrated that they are able to stimulate their own transcription through an auto-catalytic process (Chen et al., 1995; Nishimura et al., 2000; Okuno et al., 2005; Tsai et al., 1991).”
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Metadata
- Authors
- Nerlov, C., Querfurth, E., Kulessa, H., & Graf, T.
- Affiliations
- Albert Einstein College of Medicine (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2000-04-15
- Volume
- 95
- Issue
- 8
- Pages
- 2543-2551
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1504158565
- Semantic Scholar
- 121bf40998cef29230a3ff789b6f8cdfac638d0d
- Cited by
- 366
- References
- 46
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 8 · 2023: 8 · 2022: 10 · 2021: 12 · 2020: 16 · 2019: 14 · 2018: 7 · 2017: 10 · 2016: 12 · 2015: 10 · 2014: 13 · 2013: 13 · 2012: 7
- FWCI
- 6.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
- Keywords
- GATA-1, PU.1, transcriptional repression, protein-protein interaction, ETS domain, myeloid differentiation, transcription factor interaction, DNA-binding domain
- MeSH terms
- Proto-Oncogene Protein Spi-1, Cell Differentiation, Cell Line, DNA-Binding Proteins, Gene Expression Regulation, Humans, Nuclear Proteins, Proto-Oncogene Proteins, Transcription Factors, Transcription, Genetic, Trans-Activators, Gene Transfer Techniques, Leukopoiesis, Erythroid-Specific DNA-Binding Factors, GATA1 Transcription Factor
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