Originally published as Genetics Published Articles Ahead of Print on August 24, 2007.

Genetics, Vol. 177, 1621-1637, November 2007, Copyright © 2007
doi:10.1534/genetics.106.061812

A ONECUT Homeodomain Protein Communicates X Chromosome Dose to Specify Caenorhabditis elegans Sexual Fate by Repressing a Sex Switch Gene

Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3204

1 Corresponding author: Department of Molecular and Cell Biology, Howard Hughes Medical Institute, 16 Barker Hall, MC 3204, University of California, Berkeley, CA 94720-3204.
E-mail: bjmeyer{at}berkeley.edu

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.


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J. M. Gladden, B. Farboud, and B. J. Meyer
Revisiting the X:A Signal That Specifies Caenorhabditis elegans Sexual Fate
Genetics, November 1, 2007; 177(3): 1639 - 1654.
[Abstract] [Full Text] [PDF]