Genetics. Published Articles Ahead of Print: August 24, 2007, Copyright © 2007
doi:10.1534/genetics.106.061812


A more recent version of this article appeared on November 1, 2007.


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

1 University of California, Berkeley
2 University of California, Berkeley; HHMI

* To whom correspondence should be addressed. E-mail: bjmeyer{at}berkeley.edu.

Submitted on June 22, 2007
Revised on August 8, 2007
Accepted on 8 August 2007


Abstract

ABSTRACT Sex is determined in C. 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 it acts as a dose-dependent repressor of xol-1 transcript levels. Unexpectedly, other XSEs also repress xol-1 predominantly, but not exclusively, at the transcript level. The two-fold difference in X dose between XO and XX animals is translated into the male versus hermaphrodite fate by the synergistic action of multiple, independent XSEs that render xol-1 active or inactive, primarily through transcriptional regulation.

Key Words: C. elegans, dosage compensation, dose-dependent signals, homeodomain protein, sex determination




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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.
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