The formin homology 2 (FH2) domain controls actin nucleation both in vivo and in vitro. Recent structural studies provided the mechanistic basis for this activity. In a screen for mutants that affect ASE cell fate determination (see abstract by Flowers et al.), we were surprised to identify an allele of K01B6.1, a predicted gene containing a FOrmin homology 2 domain and two DNA-binding ZInc finger motifs (hence called
fozi-1).
fozi-1 alleles were also retrieved in a screen by Kelly Lius lab for genes affecting mesoderm specification. We find that
fozi-1 is expressed in a very restricted number of head neurons, including ASEL and ASER. The effect that
fozi-1 has on ASEL and ASER cell fate specification is unusual. In contrast to many other left/right asymmetry-inducing genes that we have analyzed (see abstract by Johnston et al.),
fozi-1 mutants display a "mixed" phenotype, in that ASEL fate is partially de-repressed in ASER, but ASER fate is unaffected. We find that a rescuing
fozi-1::gfp transgene localizes to the nucleus consistent with a role of
fozi-1 in gene regulation. The presence of an FH2 domain in
fozi-1 suggests that an actin interacting protein, and therefore by interference, actin, has a role in the nucleus. Recent in vitro evidence indeed indicates that actin may play a role in RNA Pol I, II and III-mediated nuclear transcription events.
fozi-1 may be the first DNA-binding protein identified to provide a direct, genetically verified link between actin and transcription.