Structural basis of simultaneous recruitment of the transcriptional regulators LMO2 and FOG1/ZFPM1 by the transcription factor GATA1

Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14443-8. doi: 10.1073/pnas.1105898108. Epub 2011 Aug 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Binding, Competitive
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • GATA1 Transcription Factor / chemistry*
  • GATA1 Transcription Factor / metabolism
  • LIM Domain Proteins
  • Metalloproteins / chemistry*
  • Metalloproteins / metabolism
  • Models, Anatomic
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism
  • Transcription, Genetic*

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • GATA1 Transcription Factor
  • GATA1 protein, human
  • LIM Domain Proteins
  • LMO2 protein, human
  • Metalloproteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Transcription Factors
  • ZFPM1 protein, human
  • DNA

Associated data

  • PDB/2L6Y
  • PDB/2L6Z