Structure and function of the Zn(II) binding site within the DNA binding domain of the GAL4 transcription factor

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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Structure and Function of the Glucocorticoid Receptor DNA-Binding Domain

Nucleic Acids and Molecular Biology ◽

10.1007/978-3-642-77950-3_7 ◽

1993 ◽

pp. 120-147

Author(s):

B. Luisi ◽

W. Xu ◽

P. Sigler

Keyword(s):

Dna Binding ◽

Glucocorticoid Receptor ◽

Structure And Function ◽

Binding Domain ◽

Dna Binding Domain ◽

And Function

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GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription

Blood ◽

10.1182/blood.v95.8.2543.008k19_2543_2551 ◽

2000 ◽

Vol 95 (8) ◽

pp. 2543-2551 ◽

Cited By ~ 11

Author(s):

Claus Nerlov ◽

Erich Querfurth ◽

Holger Kulessa ◽

Thomas Graf

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Dna Binding ◽

Direct Interaction ◽

Binding Domain ◽

Dependent Manner ◽

Dna Binding Domain ◽

Transactivation Domain ◽

Ets Domain ◽

And Function

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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