Transcriptional activators are often modulated and eventually turned off after their initial activation. While many studies have investigated transcription factor activation pathways, relatively less attention has been paid to the deactivation of these molecules. [Kodadek et al. (2006) Cell 127: 261-264]. Using a short-lived GFP driven by the
unc-4 promoter, we have examined the inactivation of this transcription factor. UNC-4 is a homeodomain protein [Miller et al. (1992) Nature 355: 841-845] that is expressed in A-type motorneurons and appears to specify their differentiation including their synaptic partners. Northern blots indicate that peak
unc-4 mRNA transcript levels occur at late L1/early L2 [Miller et al. (1995) Development 121: 2877-2886], concurrent with the developmental stage when A-type motorneurons receive synaptic input from interneurons [Miller et al. (1992) Nature 355: 841-845]. Thereafter, transcript levels fall precipitously, and adults no longer express
unc-4 mRNA. Similarly, strains carrying unstable GFP driven by the
unc-4 promoter produce GFP label in A-type motorneurons only at this L1/L2 stage. [Zhang et al. (2004) Cell 119(1): 137-44; Poyurovsky et al. (2004) Mol Cell 12(4): 875-87]. We have used this strain to screen for mutants in order to identify candidates where the
unc-4 promoter is constitutively active beyond the L1/L2 stage. A screen of 22,000 haploid genomes yielded 12 candidates where GFP fluorescence is observed in all A-type motorneurons during adult stage. A further 19 candidates showed GFP fluorescence in a subset of the A-type motorneuron during adult stage. Complementation and mapping are in progress to identify these candidates.