title: A ONECUT homeodomain protein communicates X chromosome dose to specify Caenorhabditis elegans sexual fate by repressing a sex switch gene.
abstract: Sex is determined in Caenorhabditis elegans through a dose-dependent signal that communicates the number of X chromosomes relative to the ploidy, the number of sets of autosomes. The sex switch gene xol-1 is the direct molecular target of this X:A signal and integrates both X and autosomal components to determine sexual fate. X chromosome number is relayed by X signal elements (XSEs) that act cumulatively to repress xol-1 in XX animals, thereby inducing hermaphrodite fate. Ploidy is relayed by autosomal signal elements (ASEs), which counteract the single dose of XSEs in XO animals to activate xol-1 and induce the male fate. Our goal was to identify and characterize new XSEs and further analyze known XSEs to understand the principles by which a small difference in the concentration of an intracellular signal is amplified to induce dramatically different developmental fates. We identified a new XSE, the ONECUT homeodomain protein CEH-39, and showed that it acts as a dose-dependent repressor of xol-1 transcript levels. Unexpectedly, most other XSEs also repress xol-1 predominantly, but not exclusively, at the transcript level. The twofold difference in X dose between XO and XX animals is translated into the male vs. hermaphrodite fate by the synergistic action of multiple, independent XSEs that render xol-1 active or inactive, primarily through transcriptional regulation.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3204, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Gladden
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Meyer
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002874:Chromosome Mapping; D017931:DNA Primers / Q000235:genetics; D018509:DNA, Helminth / Q000235:genetics; D004303:Dosage Compensation, Genetic; D005260:Female; D018628:Gene Dosage; D017238:Genes, Helminth; D008297:Male; D008954:Models, Biological; D051558:Onecut Transcription Factors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D019849:Sex Determination Processes; D012733:Sex Differentiation / Q000235:genetics; D015398:Signal Transduction; D014960:X Chromosome / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D018509:DNA, Helminth; D051558:Onecut Transcription Factors; C091429:XOL-1 protein, C elegans