Regulatory factor X (RFX) transcription factors are distributed and play important roles in eukaryotes. In mammals, there are five members of the RFX transcription factor family controlling a diversity of biological processes. For example RFX5 regulates major histocompatibility complex class II (MHC II) gene expression while RFX3 regulates nodal cilium development. In Caenorhabditis elegans,
daf-19 encodes the sole RFX transcription factor [1].
daf-19 mutants lack all sensory cilia and exhibit severe sensory defects.
daf-19 regulates ciliogenesis by binding to an X-box motif in the promoter of xbx genes [2].
daf-19 mutants do not express the autosomal dominant polycystic kidney disease (ADPKD) gene homolog
pkd-2, although an X-box is lacking in the
pkd-2 promoter [3]. How DAF-19 regulates both ciliogenesis and ciliated neuron differentiation and function is unknown. Here, we describe the characterization of a new allele of
daf-19,
n4132 [4], that specifically affects sensory neuron function but not ciliogenesis. We find that the
daf-19 locus encodes multiple isoforms including one that is expressed in a subset of ciliated neurons including the polycystin-expressing male-specific CEM, HOB, and RnB (not R6B) sensory neurons. Expression of this
daf-19 isoform depends on at least two separate enhancers, an RnB and HOB enhancer deleted in the
n4132 mutant and a CEM enhancer. The function of the CEM enhancer is dependent on the RnB and HOB enhancer. We propose that DAF-19 is a positive regulator of
lov-1,
pkd-2, and genes involved in male sensory neuron function and polycystin signaling. Targets of this PKD gene specific isoform of DAF-19 present new sensory components required for C. elegans male mating behavior as well as potential points of therapeutic intervention in ADPKD. 1. Swoboda P et al (2000) Molecular Cell 5;411-421 2. Efimenko E et al (2005) Development 132;1923-1934 3. Yu H et al (2003) Development 130;5217-5227 4. Johanna Varner et al (2004) East Coast Worm Meeting
pp248, we thank Hillel Schwartz and Bob Horvitz for kind gift of the
n4132 allele.