Kopczynski JB et al. (1993) International C. elegans Meeting "Regulation of xol-1 by the X:A ratio."

Meyer BJ, Kopczynski JB

[International C. elegans Meeting, 1993]

Kopczynski JB et al. (1995) International C. elegans Meeting "THE X:A RATIO, A MULTIGENIC SIGNALLING SYSTEM"

Akerib CC, Meyer BJ, Kopczynski JB

[International C. elegans Meeting, 1995]

The primary signal for sex determination is the X:A ratio. We found that three regions near the left end of X include dose-sensitive signal elements. Most XO animals with two doses of all three regions are dead; XX animals with a single dose of these regions are Dpy, indicating a dosage-compensation defect, and masculinized. Changing the dose of any one of these regions alone has little or no effect. Furthermore, other regions of X must also include signal elements. As one approach to identifying mutations in signal elements, we isolated suppressors of the XO-specific lethality caused by X duplications. Two strong suppressors, y303 and y304, map between dpy-3 and unc-2, suggesting that y303 and/or y304 might be mutations in fox-1. y303 and y304 XX animals are wild type, but XX animals heterozygous for both y303 or y304 and meDf6, which deletes at least two signal elements, are Dpy, as expected if y303 and y304 are loss-of-function mutations in a signal element. A second approach to identifying signal elements relies on the finding that xol-1, a switch gene and likely target of the X:A ratio, is sex-specifically regulated, with high levels in XO embryos and low levels in XX embryos. Using a xol-1:lacZ reporter gene as an assay, we screened for mutations that reduce the perceived X:A ratio in XX animals and thereby cause elevated expression of xol-1 in these animals. We identified two X-linked mutations: y263, which maps between unc-18 and dpy-6, and y264, which maps to the right of unc-3. y264 XX animals are slightly Dpy and Egl. y264 acts either as part of the X chromosome signal or as a regulator of xol-1, since y264 can suppress the XO-specific lethality caused by signal element duplications, but cannot suppress xol-1 mutations. Both of these approaches have proven powerful for identifying components of a multigenic signalling system.

Swain A et al. (1998) Nature "Developmental genetics. Too much sex is bad for males."

Lovell-Badge R, Swain A

[Nature, 1998]

Many species rely on chromosome-based systems-such as one X versus two X chromosomes-to trigger the differences between males and females. To do this they must find ways to count the sex chromosomes and to activate the process of dosage compensation, which corrects the imbalance of sex-linked genes. A paper by Carmi, Kopczynski and Meyer on page 168 of this issue brings us closer to understand chromosome counting in the nematode worm Caenorhabditis elegans. The authors have identified an X-linked gene that encodes a protein related to nuclear-hormone receptors. This protein, SEX-1, represses the transcription of xol-1, the pivotal gene involved in both dosage compensation and sex determination.

Carmi I et al. (1998) Nature "The nuclear hormone receptor SEX-1 is an X-chromosome signal that determines nematode sex."

Meyer BJ, Kopczynski JB, Carmi I

[Nature, 1998]

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. xol-1 specifies male (XO) fate when active and hermaphrodite (XX) fate when inactive. 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 mechanisms. 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 sexes). 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.AD - Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley 94720-3204, USA.FAU - Carmi, IAU - Carmi IFAU - Kopczynski, J BAU - Kopczynski JBFAU - Meyer, B JAU - Meyer BJLA - engSI - GENBANK/AF049869PT - Journal ArticleCY - ENGLANDTA - NatureJID - 0410462RN - 0 (Helminth Proteins)RN - 0 (Receptors, Cytoplasmic and Nuclear)RN - 0 (Repressor Proteins)RN - 0 (sex-1 protein)RN - 161477-65-2 (XOL-1 protein)SB - IM

Chin Yee Loh et al. (2001) International C. elegans Meeting "The nuclear receptor SEX-1 in C. eleganssex determination"

Barbara J Meyer, Chin Yee Loh

[International C. elegans Meeting, 2001]

In C. elegans , the primary sex determination signal that specifies the two sexes, XO males and XX hermaphrodites, is the number of X chromosomes relative to the sets of autosomes. The X-signal elements located on the X chromosome function cumulatively to repress the sex determination and dosage compensation switch gene xol-1 , whose level of expression sets the sexual fates. The X-signal element, sex-1 , encodes a nuclear receptor that transcriptionally regulates xol-1. Previously, we have identified a 2.8 kb region of the xol-1 promoter that binds SEX-1 in vivo (Carmi, 1998). A GFP reporter fused to this 2.8 kb promoter region is derepressed in a sex-1(gm41) mutant background, further suggesting that SEX-1 regulatory regions might be contained within this fragment of the xol-1 promoter. To determine whether SEX-1 binds directly to the xol-1 promoter, we are undertaking in vitro binding experiments with a partially-purified DNA-binding domain of SEX-1 and fragments of the xol-1 promoter. In these experiments, we are also interested in investigating whether SEX-1 functions as a monomer or dimer. Carmi I., Kopczynski J.B., and Meyer B.J. (1998). The nuclear hormone receptor SEX-1 is an X-chromosome signal that determines nematode sex. Nature 396 , 168-73.

Zhao Y et al. (2007) BMC Genomics "Poly-G/poly-C tracts in the genomes of Caenorhabditis."

Zhao Y, O'Neil NJ, Rose AM

[BMC Genomics, 2007]

ABSTRACT: BACKGROUND: In the genome of Caenorhabditis elegans, homopolymeric poly-G/poly-C tracts (G/C tracts) exist at high frequency and are maintained by the activity of the DOG-1 protein. The frequency and distribution of G/C tracts in the genomes of C. elegans and the related nematode, C. briggsae were analyzed to investigate possible biological roles for G/C tracts. RESULTS: In C. elegans, G/C tracts are distributed along every chromosome in a non-random pattern. Most G/C tracts are within introns or are close to genes. Analysis of SAGE data showed that G/C tracts correlate with the levels of regional gene expression in C. elegans. G/C tracts are over-represented and dispersed across all chromosomes in another Caenorhabditis species, C. briggase. However, the positions and distribution of G/C tracts in C. briggsae differ from those in C. elegans. Furthermore, the C. briggsae dog-1 ortholog CBG19723 can rescue the mutator phenotype of C. elegans dog-1 mutants. CONCLUSIONS: The abundance and genomic distribution of G/C tracts in C. elegans, the effect of G/C tracts on regional transcription levels, and the lack of positional conservation of G/C tracts in C. briggsae suggest a role for G/C tracts in chromatin structure but not in the transcriptional regulation of specific genes.

Bhagwati P Gupta et al. (2002) West Coast Worm Meeting "Genetic analysis of the vulval mutants in C. briggsae"

Shahla Gharib, Bhagwati P Gupta, Paul W Sternberg, Jennifer X Li

[West Coast Worm Meeting, 2002]

To understand the evolution of developmental mechanisms, we are doing a comparative analysis of vulval patterning in C. elegans and C. briggsae. C. briggsae is closely related to C. elegans and has identical looking vulval morphology. However, recent studies have indicated subtle differences in the underlying mechanisms of development. The recent completion of C. briggsae genome sequence by the C. elegans Sequencing Consortium is extremely valuable in identifying the conserved genes between C. elegans and C. briggsae.

Antika TR et al. (2023) J Biol Chem "Sequence-specific targeting of C. elegans C-Ala to the D-loop of tRNAAla."

Horng JC, Hsu HL, Nazilah KR, Wang CC, Wang TL, Wang SC, Antika TR, Chuang TH, Chrestella DJ, Wang SW, Tseng YK, Pan HC

[J Biol Chem, 2023]

Alanyl-tRNA synthetase (AlaRS) retains a conserved prototype structure throughout its biology. Nevertheless, its C-terminal domain (C-Ala) is highly diverged and has been shown to play a role in either tRNA or DNA binding. Interestingly, we discovered that Caenorhabditis elegans cytoplasmic C-Ala (Ce-C-Ala_c) robustly binds both ligands. How Ce-C-Ala_c targets its cognate tRNA and whether a similar feature is conserved in its mitochondrial counterpart remain elusive. We show that the N- and C-terminal subdomains of Ce-C-Ala_c are responsible for DNA and tRNA binding, respectively. Ce-C-Ala_c specifically recognized the conserved invariant base G¹⁸ in the D-loop of tRNA^Ala through a highly conserved lysine residue, K934. Despite bearing little resemblance to other C-Ala domains, C. elegans mitochondrial C-Ala (Ce-C-Ala_m) robustly bound both tRNA^Ala and DNA and maintained targeting specificity for the D-loop of its cognate tRNA. This study uncovers the underlying mechanism of how C. elegans C-Ala specifically targets the D-loop of tRNA^Ala.

Blumenthal TE et al. (1994) Worm Breeder's Gazette "C. elegans U2AF 65."

Zorio DAR, Lea K, Blumenthal TE

[Worm Breeder's Gazette, 1994]

C. elegans U2AF65

Oomura, S. et al. (2019) International Worm Meeting "Early embryogenesis of C. inopinata, a sibling species of C.elegans."

Matsumura, Y., Haruta, N., Hoshi, Y., Sugimoto, A., Oomura, S.

[International Worm Meeting, 2019]

C. inopinata is a newly discovered sibling species of C. elegans. Despite their phylogenetic closeness, they have many differences in morphology and ecology. For example, while C. elegans is hermaphroditic, C. inopinata is gonochoristic; C. inopinata is nearly twice as long as C. elegans. A comparative analysis of C. elegans and C. inopinata enables us to study how genomic changes cause these phenotypic differences. In this study, we focused on early embryogenesis of C. inopinata. First, by the microparticle bombardment method we made a C. inopinata line that express GFP::histone in whole body, and compared the early embryogenesis with C. elegans by DIC and fluorescent live imaging. We found that the position of pronuclei and polar bodies were different between these two species. In C. elegans, the female and male pronuclei first become visible in anterior and posterior sides, respectively, then they meet at the center of embryo. On the other hand, the initial position of pronuclei were more closely located in C. inopinata. Also, the polar bodies usually appear in the anterior side of embryo in C. elegans, but they appeared at random positions in C. inopinata. Therefore, we infer that C. inopinata may have a different polarity formation mechanism from that in C. elegans. We are also analyzing temperature dependency of embryogenesis in C. inopinata, whose optimal temperature is ~7 degree higher than that in C. elegans.