Ec. Svensson et al., A functionally conserved N-terminal domain of the friend of GATA-2 (FOG-2)protein represses GATA4-dependent transcription, J BIOL CHEM, 275(27), 2000, pp. 20762-20769
GATA4 is a transcriptional activator of cardiac-restricted promoters and is
required for normal cardiac morphogenesis. Friend of GATA-2 (FOG-2) is a m
ultizine finger protein that associates with GATA4 and represses GATA4-depe
ndent transcription. To better understand the transcriptional repressor act
ivity of FOG-2 we performed a functional analysis of the FOG-2 protein. The
results demonstrated that 1) zinc fingers 1 and 6 of FOG-2 are each capabl
e of interacting with evolutionarily conserved motifs within the N-terminal
zinc finger of mammalian GATA proteins, 2) a nuclear localization signal (
RKRRK) (amino acids 736-740) is required to program nuclear targeting of FO
G-2, and 3) FOG-2 can interact with the transcriptional co-repressor, C-ter
minal-binding protein-2 via a conserved sequence motif in FOG-2 (PIDLS). Su
rprisingly, however, this interaction with C-terminal-binding protein-2 is
not required for FOG-2-mediated repression of GATA4-dependent transcription
. instead, we have identified a novel N-terminal domain of FOG-2 (amino aci
ds 1-247) that is both necessary and sufficient to repress GATA4-dependent
transcription. This N-terminal repressor domain is functionally conserved i
n the related protein, Friend of GATA1, Taken together, these results defin
e a set of evolutionarily conserved mechanisms by which FOG proteins repres
s GATA-dependent transcription and thereby form the foundation for genetic
studies designed to elucidate the role of FOG-2 in cardiac development.