HIM-17 regulates the position of recombination events and GSP-1/2 localization to establish short arm identity on bivalents in meiosis

Abstract

The position of recombination events established along chromosomes in early prophase I and the chromosome remodeling that takes place in late prophase I are intrinsically linked steps of meiosis that need to be tightly regulated to ensure accurate chromosome segregation and haploid gamete formation. Here, we show that RAD-51 foci, which form at the sites of programmed meiotic DNA double-strand breaks (DSBs), exhibit a biased distribution toward off-centered positions along the chromosomes in wild-type Caenorhabditis elegans, and we identify two meiotic roles for chromatin-associated protein HIM-17 that ensure normal chromosome remodeling in late prophase I. During early prophase I, HIM-17 regulates the distribution of DSB-dependent RAD-51 foci and crossovers on chromosomes, which is critical for the formation of distinct chromosome subdomains (short and long arms of the bivalents) later during chromosome remodeling. During late prophase I, HIM-17 promotes the normal expression and localization of protein phosphatases GSP-1/2 to the surface of the bivalent chromosomes and may promote GSP-1 phosphorylation, thereby antagonizing Aurora B kinase AIR-2 loading on the long arms and preventing premature loss of sister chromatid cohesion. We propose that HIM-17 plays distinct roles at different stages during meiotic progression that converge to promote normal chromosome remodeling and accurate chromosome segregation.

Disparate roles forC. elegansDNA translocase paralogs RAD-54.L and RAD-54.B in meiotic prophase germ cells

“…Further, cytological evidence from mammalian cells supports RAD54 having both an ATP-independent activity that promotes efficient recruitment of RAD51 to DSBR sites and an ATP-dependent activity that promotes RAD51 removal (Agarwal et al, 2011;Tan et al, 1999). In C. elegans meiocytes, RAD-54.L (formerly known as RAD-54) has been shown to be essential for removal of RAD-51 from DSBR sites (Mets and Meyer, 2009;Nadarajan et al, 2021;Roelens et al, 2019b;Saito et al, 2012).…”

Widespread transposon co-option in the Caenorhabditis germline regulatory network

“…S3A). HIM-17 is a germline chromatin-associated factor important for diverse germline functions including the proliferation versus meiotic entry decision, meiotic double-strand break (DSB) formation, and germline chromatin modification (22)(23)(24)(25). It has six THAP domains, putative sequence-specific DNA binding domains shared by P-element family transposases (26).…”

“…Down-regulation of these HIM-17 targets likely accounts for the strong reduction in DSBs and the resulting high incidence of males (Him) phenotype observed in him-17 mutants (fig. S3E) (22,25). The pleiotropic effects on germline processes observed in him-17 mutants (22)(23)(24)(25)29), a factor that directly controls the activity of many co-opted promoters, highlight the biological impact of the co-option of hundreds of germline promoters in C. elegans.…”

“…S3E) (22,25). The pleiotropic effects on germline processes observed in him-17 mutants (22)(23)(24)(25)29), a factor that directly controls the activity of many co-opted promoters, highlight the biological impact of the co-option of hundreds of germline promoters in C. elegans.…”

Loss, Gain, and Retention: Mechanisms Driving Late Prophase I Chromosome Remodeling for Accurate Meiotic Chromosome Segregation

“…LAB-1, the functional analog of shugoshin, which, during earlier prophase, was localized throughout the length of the chromosomes, is restricted to the long arms by late prophase I, protecting SCC along this domain from AIR-2 phosphorylation and premature removal, by targeting GSP-1 and GSP-2 (PPI protein phosphatase homologs) to this chromosomal region [ 72 , 83 , 84 ]. In addition, the chromatin-associated protein HIM-17 has been implicated in preventing the loading of AIR-2 on the long arm of the bivalent, by regulating the expression, localization, and possibly the phosphorylation of GSP-1 and GSP-2 [ 85 ].…”