title: Structural basis of simultaneous recruitment of the transcriptional regulators LMO2 and FOG1/ZFPM1 by the transcription factor GATA1.
abstract: 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.
authors.affiliation: School of Molecular Bioscience, University of Sydney, New South Wales, 2006 Sydney, Australia.
authors.forename: Lorna
authors.initials: L
authors.lastname: Wilkinson-White
authors.forename: Roland
authors.initials: R
authors.lastname: Gamsjaeger
authors.forename: Siavoush
authors.initials: S
authors.lastname: Dastmalchi
authors.forename: Beeke
authors.initials: B
authors.lastname: Wienert
authors.forename: Philippa H
authors.initials: PH
authors.lastname: Stokes
authors.forename: Merlin
authors.initials: M
authors.lastname: Crossley
authors.forename: Joel P
authors.initials: JP
authors.lastname: Mackay
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Matthews
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001667:Binding, Competitive; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D050982:GATA1 Transcription Factor / Q000737:chemistry* / Q000378:metabolism; D060588:LIM Domain Proteins; D008667:Metalloproteins / Q000737:chemistry* / Q000378:metabolism; D008953:Models, Anatomic; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; D008667:Metalloproteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C498432:ZFPM1 protein, human; D004247:DNA