Structural basis of simultaneous recruitment of the transcriptional regulators LMO2 and FOG1/ZFPM1 by the transcription factor GATA1
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- Lorna Wilkinson-White
- School of Molecular Bioscience, University of Sydney, New South Wales, 2006 Sydney, Australia; and
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- Roland Gamsjaeger
- School of Molecular Bioscience, University of Sydney, New South Wales, 2006 Sydney, Australia; and
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- Siavoush Dastmalchi
- School of Molecular Bioscience, University of Sydney, New South Wales, 2006 Sydney, Australia; and
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- Beeke Wienert
- School of Molecular Bioscience, University of Sydney, New South Wales, 2006 Sydney, Australia; and
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- Philippa H. Stokes
- School of Molecular Bioscience, University of Sydney, New South Wales, 2006 Sydney, Australia; and
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- Merlin Crossley
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, 2052 Sydney, Australia
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- Joel P. Mackay
- School of Molecular Bioscience, University of Sydney, New South Wales, 2006 Sydney, Australia; and
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- Jacqueline M. Matthews
- School of Molecular Bioscience, University of Sydney, New South Wales, 2006 Sydney, Australia; and
説明
<jats:p>The control of red blood cell and megakaryocyte development by the regulatory protein GATA1 is a paradigm for transcriptional regulation of gene expression in cell lineage differentiation and maturation. Most GATA1-regulated events require GATA1 to bind FOG1, and essentially all GATA1-activated genes are cooccupied by a TAL1/E2A/LMO2/LDB1 complex; however, it is not known whether FOG1 and TAL1/E2A/LMO2/LDB1 are simultaneously recruited by GATA1. Our structural data reveal that the FOG1-binding domain of GATA1, the N finger, can also directly contact LMO2 and show that, despite the small size (< 50 residues) of the GATA1 N finger, both FOG1 and LMO2 can simultaneously bind this domain. LMO2 in turn can simultaneously contact both GATA1 and the DNA-binding protein TAL1/E2A at bipartite E-box/WGATAR sites. Taken together, our data provide the first structural snapshot of multiprotein complex formation at GATA1-dependent genes and support a model in which FOG1 and TAL1/E2A/LMO2/LDB1 can cooccupy E-box/WGATAR sites to facilitate GATA1-mediated activation of gene activation.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 108 (35), 14443-14448, 2011-08-15
Proceedings of the National Academy of Sciences