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First published online November 11, 2009
doi: 10.1242/10.1242/dev.034637

Development 136, 3881-3887 (2009)
Published by The Company of Biologists 2009
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xol-1, the master sex-switch gene in C. elegans, is a transcriptional target of the terminal sex-determining factor TRA-1

Balázs Hargitai1, Vera Kutnyánszky1, Timothy A. Blauwkamp2, Attila Steták3, Györgyi Csankovszki2, Krisztina Takács-Vellai1 and Tibor Vellai1,*

1 Department of Genetics, Eötvös Loránd University, Budapest H-1117, Hungary
2 Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA
3 Division of Molecular Psychology, Life Sciences Training Facility, Biozentrum, University of Basel, Basel CH-4056, Switzerland

* Author for correspondence (vellai{at}falco.elte.hu)

Accepted September 22, 2009

In the nematode Caenorhabditis elegans, sex is determined by the ratio of X chromosomes to sets of autosomes: XX animals (2X:2A=1.0) develop as hermaphrodites and XO animals (1X:2A=0.5) develop as males. TRA-1, the worm ortholog of Drosophila Cubitus interruptus and mammalian Gli (Glioma-associated homolog) proteins, is the terminal transcription factor of the C. elegans sex-determination pathway, which specifies hermaphrodite fate by repressing male-specific genes. Here we identify a consensus TRA-1 binding site in the regulatory region of xol-1, the master switch gene controlling sex determination and dosage compensation. xol-1 is normally expressed in males, where it promotes male development and prevents dosage compensation. We show that TRA-1 binds to the consensus site in the xol-1 promoter in vitro and inhibits the expression of xol-1 in XX animals in vivo. Furthermore, inactivation of tra-1 enhances, whereas hyperactivation of tra-1 suppresses, lethality in animals with elevated xol-1 activity. These data imply the existence of a regulatory feedback loop within the C. elegans sex-determination and dosage-compensation cascade that ensures the accurate dose of X-linked genes in cells destined to adopt hermaphrodite fate.

Key words: Sex determination, Dosage compensation, Caenorhabditis elegans, TRA-1/Gli/Ci, xol-1, Chromatin


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