Abstract
AbstractThe 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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Dates
Type | When |
---|---|
Created | 5 years, 10 months ago (Oct. 14, 2019, 12:04 a.m.) |
Deposited | 1 year, 11 months ago (Sept. 21, 2023, 12:06 p.m.) |
Indexed | 2 weeks, 1 day ago (Aug. 21, 2025, 12:51 p.m.) |
Issued | 25 years, 4 months ago (April 15, 2000) |
Published | 25 years, 4 months ago (April 15, 2000) |
Published Print | 25 years, 4 months ago (April 15, 2000) |
@article{Nerlov_2000, title={GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription}, volume={95}, ISSN={0006-4971}, url={http://dx.doi.org/10.1182/blood.v95.8.2543}, DOI={10.1182/blood.v95.8.2543}, number={8}, journal={Blood}, publisher={American Society of Hematology}, author={Nerlov, Claus and Querfurth, Erich and Kulessa, Holger and Graf, Thomas}, year={2000}, month=apr, pages={2543–2551} }