X Chromosome Crossover Formation and Genome Stability inCaenorhabditis elegansAre Independently Regulated byxnd-1

Abstract

The germ line efficiently combats numerous genotoxic insults to ensure the high fidelity propagation of unaltered genomic information across generations. Yet, germ cells in most metazoans also intentionally create double-strand breaks (DSBs) to promote DNA exchange between parental chromosomes, a process known as crossing over. Homologous recombination is employed in the repair of both genotoxic lesions and programmed DSBs, and many of the core DNA repair proteins function in both processes. In addition, DNA repair efficiency and crossover (CO) distribution are both influenced by local and global differences in chromatin structure, yet the interplay between chromatin structure, genome integrity, and meiotic fidelity is still poorly understood. We have used the xnd-1 mutant of Caenorhabditis elegans to explore the relationship between genome integrity and crossover formation. Known for its role in ensuring X chromosome CO formation and germ line development, we show that xnd-1 also regulates genome stability. xnd-1 mutants exhibited a mortal germ line, high embryonic lethality, high incidence of males, and sensitivity to ionizing radiation. We discovered that a hypomorphic allele of mys-1 suppressed these genome instability phenotypes of xnd-1, but did not suppress the CO defects, suggesting it serves as a separation-of-function allele. mys-1 encodes a histone acetyltransferase, whose homolog Tip60 acetylates H2AK5, a histone mark associated with transcriptional activation that is increased in xnd-1 mutant germ lines, raising the possibility that thresholds of H2AK5ac may differentially influence distinct germ line repair events. We also show that xnd-1 regulated him-5 transcriptionally, independently of mys-1, and that ectopic expression of him-5 suppressed the CO defects of xnd-1. Our work provides xnd-1 as a model in which to study the link between chromatin factors, gene expression, and genome stability.

Leagues of their own: sexually dimorphic features of meiotic prophase I

“…This study showed that recombination is largely suppressed in the central and distal chromosomal regions and enriched in what is considered the chromosome “arms” in C. elegans (Rockman and Kruglyak 2009), although the position of these crossovers varies widely on the autosomes (Rockman and Kruglyak 2009). Moreover, multiple studies have shown that during oogenesis, DSB formation and crossing over requires histone acetylation and methylation modifications (Wagner et al 2010; McClendon et al 2016; Bessler et al 2007, 2010; Reddy and Villeneuve 2004). Currently, it is unclear whether post-translation modifications of histones are required for DSB formation and crossing over during spermatogenesis.…”

The Germline-Specific Factor OEF-1 Facilitates Coordinated Progression Through Germ Cell Development in Caenorhabditis elegans

“…Since HIM-5 and XND-1 exhibit the same autosomal localization and loss at late pachytene as OEF-1, we analyzed the broods of oef-1; him-5 and xnd-1; oef-1 double-mutants. Given that xnd-1 mutants have pleiotropic germline defects and show stochastic sterility in later generations (McClendon et al 2016), we focused our analyses on the broods of xnd-1 M+Z-parents. We found that oef-1 partially rescued the him-5 percentage of males from 37.53 to 30.24% (P , 0.0001, Fisher's exact test) (Table 1).…”

Chromosome Integrity is Required for the Initiation of Meiotic Sex Chromosome Inactivation inCaenorhabditis elegans

“…First, silencing of unsynapsed chromatin has been observed in C. elegans 32 , so the basic mechanism of MSUC exists. Second, disruption of sex chromosome integrity in mammals leads to silencing of synapsed parts of autosomes and sex chromosomes in pachytene [34][35][36] Like initiation of silencing, other meiotic processes are also executed differently on the X chromosome than on autosomes in hermaphroditic worms [81][82][83][84][85][86] . These differences suggest that the X chromosome is marked differently than the autosomes, and, indeed, previous reports indicate that the X chromosomes are enriched with different histone modifications than are autosomes 26,32,81,82,87 .…”

“…Like initiation of silencing, other meiotic processes are also executed differently on the X chromosome than on autosomes in hermaphroditic worms 81–86 . These differences suggest that the X chromosome is marked differently than the autosomes, and, indeed, previous reports indicate that the X chromosomes are enriched with different histone modifications than are autosomes 26, 32, 81, 82, 87 . Thus, an epigenetic mechanism may regulate silencing and its dependence on integrity.…”