| 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. |