Academic journal article Genetics

A Single Unpaired and Transcriptionally Silenced X Chromosome Locally Precludes Checkpoint Signaling in the Caenorhabditis Elegans Germ Line

Academic journal article Genetics

A Single Unpaired and Transcriptionally Silenced X Chromosome Locally Precludes Checkpoint Signaling in the Caenorhabditis Elegans Germ Line

Article excerpt

ABSTRACT

In many organisms, female and male meiosis display extensive sexual dimorphism in the temporal meiotic program, the number and location of recombination events, sex chromosome segregation, and checkpoint function. We show here that both meiotic prophase timing and germ-line apoptosis, one output of checkpoint signaling, are dictated by the sex of the germ line (oogenesis vs. spermatogenesis) in Caenorhabditis elegans. During oogenesis in feminized animals (fem-3), a single pair of asynapsed autosomes elicits a checkpoint response, yet an unpaired X chromosome fails to induce checkpoint activation. The single X in males and fem-3 worms is a substrate for the meiotic recombination machinery and repair of the resulting double strand breaks appears to be delayed compared with worms carrying paired X chromosomes. Synaptonemal complex axial HORMA domain proteins, implicated in repair of meiotic double strand breaks (DSBs) and checkpoint function, are assembled and disassembled on the single X similarly to paired chromosomes, but the central region component, SYP-1, is not loaded on the X chromosome in males. In fem-3 worms some X chromosomes achieve nonhomologous self-synapsis; however, germ cells with SYP-1-positive X chromosomes are not preferentially protected from apoptosis. Analyses of chromatin and X-linked gene expression indicate that a single X, unlike asynapsed X chromosomes or autosomes, maintains repressive chromatin marks and remains transcriptionally silenced and suggests that this state locally precludes checkpoint signaling.

IN metazoans, sexual dimorphisms manifest not only striking morphological somatic forms but also distinct differences in female andmale germ-line biology. In the germ line, meiosis is coupled to cellular differentiation programs that result in the production of two very distinct sex-specific haploid gamete types, oocytes and sperm. The regulation of meiosis can differ considerably between the sexes as reflected in both the phenotypic manifestations of mutants as well as the temporal program of events (Hunt and Hassold 2002; Morelli and Cohen 2005). For example, female mammals enter prophase in utero whereas males initiate prophase postnatally (Handel and Eppig 1998). In the nematode Caenorhabditis elegans prophase I for oogenesis in hermaphrodites (functionally female) takes twice as long as prophase I for spermatogenesis in males ( Jaramillo-Lambert et al. 2007). Furthermore, female germ cells of many species initiate a meiotic arrest during prophase I that does not occur in male germ cells (Masui and Clarke 1979; Eppig et al. 1996; McCarter et al. 1999). In late meiotic prophase, chromosome morphology (Shakes et al. 2009), chromatin compaction (Wu and Chu 2008), and the presence of centriole-containing centrosomes (Manandhar et al. 2005; Shakes et al. 2009; Wignall and Villeneuve 2009) can also exhibit sex-specific differences.

With some exceptions, early events in meiotic prophase such as chromosome pairing and synapsis, the close alignment of homologous chromosomes through the elaboration of the synaptonemal complex (SC), are largely conserved between the sexes; however, the extent of genetic exchange can differ significantly. Meiotic recombination rates are higher in females compared to males in humans (Donis-Keller et al. 1987), mice (Blank et al. 1988), zebrafish (Singer et al. 2002), Drosophila (Morgan 1912), and C. elegans (Zetka and Rose 1990; Meneely et al. 2002). In virtually all of these organisms, however, sex not only affects the rate of recombination but also influences the placement of exchange events along the length of the chromosome. Too few, or inappropriately placed recombination events can lead to chromosome nondisjunction (Koehler et al. 1996; Lamb et al. 1996; Ross et al. 1996). In humans meiotic failure rates as measured by aneuploidy are higher in oocytes (up to 25%) than in sperm (2%) (Hassold and Hunt 2001). It has been proposed that checkpoints monitoring meiotic events such as recombination are less stringent in females compared to males. …

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