Synaptonemal Complex Components Persist at Centromeres and Are Required for Homologous Centromere Pairing in Mouse Spermatocytes

Abstract

Recent studies in simple model organisms have shown that centromere pairing is important for ensuring high-fidelity meiotic chromosome segregation. However, this process and the mechanisms regulating it in higher eukaryotes are unknown. Here we present the first detailed study of meiotic centromere pairing in mouse spermatogenesis and link it with key events of the G2/metaphase I transition. In mouse we observed no evidence of the persistent coupling of centromeres that has been observed in several model organisms. We do however find that telomeres associate in non-homologous pairs or small groups in B type spermatogonia and pre-leptotene spermatocytes, and this association is disrupted by deletion of the synaptonemal complex component SYCP3. Intriguingly, we found that, in mid prophase, chromosome synapsis is not initiated at centromeres, and centromeric regions are the last to pair in the zygotene-pachytene transition. In late prophase, we first identified the proteins that reside at paired centromeres. We found that components of the central and lateral element and transverse filaments of the synaptonemal complex are retained at paired centromeres after disassembly of the synaptonemal complex along diplotene chromosome arms. The absence of SYCP1 prevents centromere pairing in knockout mouse spermatocytes. The localization dynamics of SYCP1 and SYCP3 suggest that they play different roles in promoting homologous centromere pairing. SYCP1 remains only at paired centromeres coincident with the time at which some kinetochore proteins begin loading at centromeres, consistent with a role in assembly of meiosis-specific kinetochores. After removal of SYCP1 from centromeres, SYCP3 then accumulates at paired centromeres where it may promote bi-orientation of homologous centromeres. We propose that, in addition to their roles as synaptonemal complex components, SYCP1 and SYCP3 act at the centromeres to promote the establishment and/or maintenance of centromere pairing and, by doing so, improve the segregation fidelity of mammalian meiotic chromosomes.

Superresolution imaging reveals structurally distinct periodic patterns of chromatin along pachytene chromosomes

“…4A) are both in range of 1-1.5 μm. Moreover, we note that in some images, the two SC strands seem to move apart at the presumed noncentromeric end, as observed previously (27). We have not observed such splitting at the presumed centromeric ends (Fig.…”

Meiosis-specific cohesin mediates homolog recognition in mouse spermatocytes

“…might initiate at different sites among organisms, there are conflicting reports in mice. Some reports suggest that the telomere is the initiation site for pairing/synapsis, while others suggest interstitial sites on the chromosome arms (Bisig et al 2012;Qiao et al 2012;Boateng et al 2013). Our point probe FISH assays indicate that the timing of homolog pairing/synapsis is similar between the arm and subtelomeric regions in wild-type and Spo11 knockout spermatocytes (Figs.…”

The Tetrahymena meiotic chromosome bouquet is organized by centromeres and promotes interhomolog recombination

“…An analogous situation exists in Drosophila oocytes, where centromere clusters form early in prophase and are synapsis initiation sites (Takeo et al, 2011;Tanneti et al, 2011). Often, pairing not only begins at the centromere, but is also most persistent in this region (Qiao et al, 2012;Bisig et al, 2012; for older reports see Stewart and Dawson, 2008). Enduring centromere pairing may support proper disjunction after the dissolution of the synaptonemal complex and/or serve as a backup connection in achiasmatic bivalents (Stewart and Dawson, 2008).…”