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

Abstract

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.

An MLL/COMPASS subunit functions in the C. elegans dosage compensation complex to target X chromosomes for transcriptional regulation of gene expression

“…Mutations in dpy-30 cause XX-specific lethality (Hsu and Meyer 1994;Hsu et al 1995) and prevent all DCC components, except SDC-2, from assembling onto hermaphrodite X chromosomes, as shown by immunofluorescence studies (Chuang et al 1996;Lieb et al 1996Lieb et al , 1998Davis and Meyer 1997;Dawes et al 1999;Yonker and Meyer 2003). Unlike most DC genes, dpy-30 functions in other developmental processes-including vulval development, male mating behavior, and aging-suggesting that dpy-30 might also function in a second gene regulatory capacity (Hsu and Meyer 1994;Greer et al 2010).…”

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

“…dpy-21 suppressed rict-1 developmental delay in a reverse genetic, RNAi screen of candidate SGK-1 targets. dpy-21 has been broadly characterized in C. elegans as a member of the DCC, which is involved in downregulation of the hermaphroditic X chromosome by 50% in order to prevent overexpression of potentially toxic Xlinked genes (Yonker and Meyer, 2003;Meyer, 2005 Time (hours) Fig. 5. dpy-21 RNAi acts non-canonically to suppress rict-1 male developmental delay.…”

“…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). The additional five associated members are SDC-1, SDC-2, SDC-3, DPY-30 and DPY-21 (Hodgkin, 1987;Hsu and Meyer, 1994;Lieb et al, 1996;Yonker and Meyer, 2003). In this work, we show that DPY-21 is most likely to be working via its role in the DCC as RNAi directed towards each DCC member tested had suppressive effects on rict-1 phenotypes.…”

A ONECUT Homeodomain Protein Communicates X Chromosome Dose to SpecifyCaenorhabditis elegansSexual Fate by Repressing a Sex Switch Gene

“…In XX animals, where xol-1 is repressed, SDC-2 induces hermaphrodite development by repressing the male-specific sex-determination gene her-1 and by triggering assembly of the dosage compensation complex (DCC) on both X chromosomes to repress transcript levels. The DCC includes two other SDC proteins and at least seven other dosage compensation proteins, five of which resemble the components of condensin, a conserved protein complex required for mitotic and meiotic chromosome compaction, resolution, and segregation Meyer 1987, 1990;Nusbaum and Meyer 1989;Nonet and Meyer 1991;Delong et al 1993;Chuang et al 1994;Hsu and Meyer 1994;Lieb et al 1996Lieb et al , 1998Davis and Meyer 1997;Kimura and Hirano 1997;Dawes et al 1999;Hirano 1999;Chu et al 2002;Yonker and Meyer 2003;M. Albrecht, C. Hassig, C. Tsai and B. Meyer, unpublished results).…”