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The nuclear hormone receptor SEX-1 is an X-chromosome signal that determines nematode sex

Nature volume 396, pages 168–173 (1998)Cite this article

Abstract

Organisms in many phyla determine sexual fate by distinguishing one X chromosome from two. Here we use the model organism Caenorhabditis elegans to dissect such an X-chromosome-counting mechanism in molecular detail. In this nematode, several genes on the X chromosome called X signal elements communicate X-chromosome dose by controlling the activity of the sex-determination gene xol-1 (refs 1, 2). xol-1 specifies male (XO) fatewhen active and hermaphrodite (XX) fate when inactive3,4. The only X signal element described so far represses xol-1 post-transcriptionally, but xol-1 is repressed in XX animals by transcriptional and post-transcriptional mechanisms2. Here we identify a nuclear-hormone-receptor homologue, SEX-1, that regulates the transcription of xol-1. We show that sex-1 is vital to X-chromosome counting: changing sex-1 gene dose in XX or XO embryos causes sexual transformation and death from inadequate dosage compensation (the hermaphrodite-specific process that equalizes X-gene expression between the sexes5). The SEX-1 protein acts directly on xol-1, associating with its promoter in vivo and repressing xol-1 transcription in XX embryos. Thus, xol-1 is the direct molecular target of the primary sex-determination signal, and the dose of a nuclear hormone receptor helps to communicate X-chromosome number to determine nematode sex.

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Figure 1: sex-1 represses xol-1 transcription in XX animals.
Figure 2: The molecular nature of sex-1.
Figure 3: The temporal and spatial expression of SEX-1 are consistent with its roleas an X signal element that represses xol-1 transcription.
Figure 4: SEX-1 localizes to extrachromosomal DNA arrays containing xol-1 promoter sequences.

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Acknowledgements

We thank G. Garriga and P. Baum for providing gm41; A. Gonzalez-Serrichio and P.Sternberg for the concept of GFP-tagged arrays and for pPD49-78; J. Lieb for suggesting the use of tagged arrays to analyse protein–DNA interactions; D. Lapidus and P. Woronoff for help with figures; A.Sluder and H. Stunnenberg for advice on SEX-1 sequence analysis; and T. Cline, H. Dawes, J. Lieb, M.Nicoll, D. Reiner and J. Rine for advice and comments on the manuscript. This work was supported bya grant from the NIH. I.C. is a Howard Hughes Medical Institute Predoctoral Fellow. B.J.M. is an investigator of the Howard Hughes Medical Institute.

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  1. Jennifer B. Kopczynski

    Present address: Exelixis Pharmaceuticals, Inc., 260 Littlefield Avenue, South San Francisco, California, 94080, USA

Authors and Affiliations

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

    Ilil Carmi, Jennifer B. Kopczynski & Barbara J. Meyer

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Correspondence to Barbara J. Meyer.

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Carmi, I., Kopczynski, J. & Meyer, B. The nuclear hormone receptor SEX-1 is an X-chromosome signal that determines nematode sex. Nature 396, 168–173 (1998). https://doi.org/10.1038/24164

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