Genes that implement the hermaphrodite mode of dosage compensation in Caenorhabditis elegans.

Abstract

We report a genetic characterization of several essential components of the dosage compensation process in Caenorhabditis elegans. Mutations in the genes dpy-26, dpy-27, dpy-28, and the newly identified gene dpy-29 disrupt dosage compensation, resulting in elevated X-linked gene expression in XX animals and an incompletely penetrant maternal-effect XX-specific lethality. These dpy mutations appear to cause XX animals to express each set of X-linked genes at a level appropriate for XO animals. XO dpy animals are essentially wild type. Both the viability and the level of X-linked gene expression in XX animals carrying mutations in two or more dpy genes are the same as in animals carrying only a single mutation, consistent with the view that these genes act together in a single process (dosage compensation). To define a potential time of action for the gene dpd-28 we performed reciprocal temperature-shift experiments with a heat sensitive allele. The temperature-sensitive period for lethality begins 5 hr after fertilization at the 300-cell stage and extends to about 9 hr, a point well beyond the end of cell proliferation. This temperature-sensitive period suggests that dosage compensation is functioning in XX animals by mid-embryogenesis, when many zygotically transcribed genes are active. While mutations in the dpy genes have no effect on the sexual phenotype of otherwise wild-type XX or XO animals, they do have a slight feminizing effect on animals whose sex-determination process is already genetically perturbed. The opposite directions of the feminizing effects on sex determination and the masculinizing effects on dosage compensation caused by the dpy mutations are inconsistent with the wild-type dpy genes acting to coordinately control both processes. Instead, the feminizing effects are most likely an indirect consequence of disruptions in dosage compensation caused by the dpy mutations. Based on the cumulative evidence, the likely mechanism of dosage compensation in C. elegans involves reducing X-linked gene expression in XX animals to equal that in XO animals via the action of the dpy genes.

Condensin restructures chromosomes in preparation for meiotic divisions

“…Y39A1B.3 (M r of 160 kD) encodes the dosage compensation protein DPY-28, a homologue of the condensin I non-SMC subunit CAP-D2 (Fig. 1 Plenefisch et al, 1989;Tsai, C., M. Albrecht, and B. Meyer, personal communication). Y110A7A.1 (M r of 200 kD) encodes HCP-6, a homologue of the condensin II non-SMC subunit CAP-D3 (Fig.…”

“…1 B, lanes 2 and 3). DPY-28 and HCP-6 are not functionally redundant during embryogenesis because both proteins are essential for viability and the terminal mutant phenotypes are distinct (see below; Plenefisch et al, 1989;Stear and Roth, 2002). The similarities of DPY-28 to CAP-D2 and DPY-26 to the condensin I subunit CAP-H/Barren (Lieb et al, 1996) suggest that a condensin-I-like complex was preserved in C. elegans and coopted to implement dosage compensation.…”

Isolation of dominant XO-feminizing mutations in Caenorhabditis elegans: new regulatory tra alleles and an X chromosome duplication with implications for primary sex determination.

“…The strain CB4919, genotype tru-2(e2046); d@-28(yI), was constructed and behaves as expected from the properties of its constituent mutations (HODGKIN 1986;PLENEFISCH et al 1989). At 15" the temperature-sensitive mutation y l has only a slightly deleterious effect and the strain grows as well as a population of 50% female, 50% male animals, as a result of the XX-feminizing properties of tru-Z(e2046).…”

“…Eliminating their activity has no effect on X 0 animals but is usually lethal to X X animals, presumably because of X chromosome overexpression (HODGKIN 1983(HODGKIN , 1987bPLENEFISCH et al 1989;Hsu and MEYER 1994). Conversely, inappropriately expressing these genes in X 0 animals (via a xol-1 mutation) leads to lethality from presumed underexpression of the X chromosome (MILLER et al 1988).…”

Inducible degradation of dosage compensation protein DPY-27 facilitates isolation of Caenorhabditis elegans males for molecular and biochemical analyses

“…Here we describe a new method to isolate relatively pure populations of males in large numbers. This method takes advantage of the inducible degradation of DPY-27, a component of the dosage compensation complex (DCC) (Plenefisch, DeLong, and Meyer 1989). In C. elegans, the DCC down regulates gene expression from the two X chromosomes in hermaphrodites such that the overall level is comparable to the expression from the single X chromosome in males.…”