Caenorhabditis elegans compensates for the difference in X chromosome dosage between the sexes by regulating transcript levels

Meyer, Barbara J; Casson, Lawrence P.

doi:10.1016/0092-8674(86)90802-0

Cited by 145 publications

(100 citation statements)

References 30 publications

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“…Dosage compensation (DC) is an evolutionarily conserved mechanism between mammals, flies and invertebrates for balancing sex chromosome expression between genders (Lyon, 1961;Meyer and Casson, 1986). In C. elegans, five proteins are involved in the core DCC, which is structurally similar to the condensin 1 complex: DPY-26, DPY-27, DPY-28, MIX-1 and CAPG-1 (Csankovszki et al, 2004;Meyer, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…X chromosomal dosage compensation (DC) has evolved in order to equalize the expression of the X-linked genes between males and females. The mechanisms by which DC occurs varies greatly between species: mammals transcriptionally mute expression of one of the two female X chromosomes (Lyon, 1961), flies double the expression of the single male X chromosome (Gelbart and Kuroda, 2009) and the C. elegans hermaphrodite downregulates gene expression from both X chromosomes by 50% (Meyer and Casson, 1986). This X chromosomal regulation is orchestrated through the dosage compensation complex (DCC).…”

Section: Introductionmentioning

confidence: 99%

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A non-canonical role for the C. elegans dosage compensation complex in growth and metabolic regulation downstream of TOR complex 2

Webster

Douglas

et al. 2013

Development

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SUMMARYThe target of rapamycin complex 2 (TORC2) pathway is evolutionarily conserved and regulates cellular energetics, growth and metabolism. Loss of function of the essential TORC2 subunit Rictor (RICT-1) in Caenorhabditis elegans results in slow developmental rate, reduced brood size, small body size, increased fat mass and truncated lifespan. We performed a rict-1 suppressor RNAi screen of genes encoding proteins that possess the phosphorylation sequence of the AGC family kinase SGK, a key downstream effector of TORC2. Only RNAi to dpy-21 suppressed rict-1 slow developmental rate. DPY-21 functions canonically in the ten-protein dosage compensation complex (DCC) to downregulate the expression of X-linked genes only in hermaphroditic worms. However, we find that dpy-21 functions outside of its canonical role, as RNAi to dpy-21 suppresses TORC2 mutant developmental delay in rict-1 males and hermaphrodites. RNAi to dpy-21 normalized brood size and fat storage phenotypes in rict-1 mutants, but failed to restore normal body size and normal lifespan. Further dissection of the DCC via RNAi revealed that other complex members phenocopy the dpy-21 suppression of rict-1, as did RNAi to the DCC effectors set-1 and set-4, which methylate histone 4 on lysine 20 (H4K20). TORC2/rict-1 animals show dysregulation of H4K20 mono-and tri-methyl silencing epigenetic marks, evidence of altered DCC, SET-1 and SET-4 activity. DPY-21 protein physically interacts with the protein kinase SGK-1, suggesting that TORC2 directly regulates the DCC. Together, the data suggest non-canonical, negative regulation of growth and reproduction by DPY-21 via DCC, SET-1 and SET-4 downstream of TORC2 in C. elegans.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A non-canonical role for the C. elegans dosage compensation complex in growth and metabolic regulation downstream of TOR complex 2

Webster

Douglas

et al. 2013

Development

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“…Paradoxically, of five X-linked genes assayed, dpy-21 mutations caused an elevation in transcript levels from four (Meneely and Wood, 1987;Meyer and Casson, 1986) and a reduction in transcript levels from one (DeLong et al, 1987). Despite their altered transcript levels, dpy-21 mutant XO males appear phenotypically wild type.…”

Section: Dpy-21 Is Expressed In Males But Fails To Localize To the Smentioning

confidence: 99%

“…dpy-21 is also required for dosage compensation; however, dpy-21 differs significantly from other dosage compensation genes. Like mutations in other dosage compensation genes, dpy-21 mutations cause elevated X-linked gene expression and morphological phenotypes dependent upon X-chromosome dose: XO animals appear wild type, while XX animals are dumpy and egg-laying defective (L. DeLong, PhD thesis, Massachusetts Institute of Technology, 1990) (DeLong et al, 1987;Hodgkin, 1983;Meneely and Wood, 1984;Meneely and Wood, 1987;Meyer and Casson, 1986;Plenefisch et al, 1989). But unlike other dosage compensation mutations, which disrupt the stability or X-localization of the dosage compensation complex, causing extensive XX-specific lethality, dpy-21 mutations, shown here to be null, cause no embryonic lethality and only infrequent larval lethality (Chuang et al, 1996;Lieb et al, 1998;Lieb et al, 1996;Plenefisch et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Recruitment ofC. elegansdosage compensation proteins for gene-specific versus chromosome-wide repression

Yonker

Meyer

2003

Development

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In C. elegans, an X-chromosome-wide regulatory process compensates for the difference in X-linked gene dose between males (XO) and hermaphrodites(XX) by equalizing levels of X-chromosome transcripts between the sexes. To achieve dosage compensation, a large protein complex is targeted to the X chromosomes of hermaphrodites to reduce their expression by half. This repression complex is also targeted to a single autosomal gene, her-1. By silencing this male-specific gene, the complex induces hermaphrodite sexual development. Our analysis of the atypical dosage compensation gene dpy-21 revealed the first molecular differences in the complex that achieves gene-specific versus chromosome-wide repression. dpy-21 mutations, shown here to be null, cause elevated X-linked gene expression in XX animals, but unlike mutations in other dosage compensation genes, they do not cause extensive XX-specific lethality or disrupt the stability or targeting of the dosage compensation complex to X. Nonetheless,DPY-21 is a member of the dosage compensation complex and localizes to X chromosomes in a hermaphrodite-specific manner. However, DPY-21 is the first member of the dosage compensation complex that does not also associate with her-1. In addition to a difference in the composition of the complex at her-1 versus X, we also found differences in the targeting of the complex to these sites. Within the complex, SDC-2 plays the lead role in recognizing X-chromosome targets, while SDC-3 plays the lead in recognizing her-1 targets.

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“…Similarly, Drosophila species equalize gene expression on the X chromosome by unilaterally upregulating X-chromosome expression in males, which simultaneously equalizes dosage effects between males and females, and between the single male X and the diploid autosomes (Lucchesi et al, 2005;Gupta et al, 2006). Caenorhabditis also has a unique dosage compensating mechanism, upregulating X-linked genes in both sexes to achieve X:autosome parity for males, and downregulating the two (now overexpressed) X chromosomes in hermaphrodites to balance the X and autosomes (Meyer and Casson, 1986;Meyer et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

All dosage compensation is local: Gene-by-gene regulation of sex-biased expression on the chicken Z chromosome

2008

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Caenorhabditis elegans compensates for the difference in X chromosome dosage between the sexes by regulating transcript levels

Cited by 145 publications

References 30 publications

A non-canonical role for the C. elegans dosage compensation complex in growth and metabolic regulation downstream of TOR complex 2

A non-canonical role for the C. elegans dosage compensation complex in growth and metabolic regulation downstream of TOR complex 2

Recruitment ofC. elegansdosage compensation proteins for gene-specific versus chromosome-wide repression

All dosage compensation is local: Gene-by-gene regulation of sex-biased expression on the chicken Z chromosome

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