Abstract
Recombination, synapsis, chromosome segregation and gene expression are co-ordinately regulated during meiosis to ensure successful execution of this specialised cell division. Studies with multiple mutant mouse lines have shown that mouse spermatocytes possess quality control checkpoints that eliminate cells with persistent defects in chromosome synapsis. In addition, studies on Trip13mod/mod mice suggest that pachytene spermatocytes that successfully complete chromosome synapsis can undergo meiotic arrest in response to defects in recombination. Here, we present additional support for a meiotic recombination-dependent checkpoint using a different mutant mouse line, Tex19.1−/−. The appearance of early recombination foci is delayed in Tex19.1−/− spermatocytes during leptotene/zygotene, but some Tex19.1−/− spermatocytes still successfully synapse their chromosomes and we show that these spermatocytes are enriched for early recombination foci. Furthermore, we show that patterns of axis elongation, chromatin modifications and histone H1t expression are also all co-ordinately skewed towards earlier substages of pachytene in these autosomally synapsed Tex19.1−/− spermatocytes. We also show that this skew towards earlier pachytene substages occurs in the absence of elevated spermatocyte death in the population, that spermatocytes with features of early pachytene are present in late stage Tex19.1−/− testis tubules and that the delay in histone H1t expression in response to loss of Tex19.1 does not occur in a Spo11 mutant background. Taken together, these data suggest that a recombination-dependent checkpoint may be able to modulate pachytene progression in mouse spermatocytes to accommodate some types of recombination defect.
Highlights
Meiosis is a central feature of the life cycle of sexually reproducing organisms that requires co-ordinated regulation of multiple distinct processes including recombination, chromosome synapsis, chromosome segregation and changes in gene expression, to generate haploid germ cells
We show that recombination dynamics, chromosome axis elongation, chromatin modifications and histone H1t expression are co-ordinately altered in Tex19.1−/− spermatocytes and that the altered pachytene progression of Tex19.1−/− spermatocytes depends on Spo11
These early recombination defects are accompanied by autosomal synapsis defects in approximately two thirds of the Tex19.1−/− pachytene spermatocytes (Crichton et al 2017), but the remaining fully synapsed pachytene spermatocytes presumably possessed sufficient recombination foci to promote a successful homology search, and do not have any confounding autosomal asynapsis that would interfere with analysing the effects of delayed recombination on meiotic progression
Summary
Meiosis is a central feature of the life cycle of sexually reproducing organisms that requires co-ordinated regulation of multiple distinct processes including recombination, chromosome synapsis, chromosome segregation and changes in gene expression, to generate haploid germ cells In meiotic spermatocytes in the mouse testis, there is strong evidence that extensive defects in meiotic chromosome synapsis can activate a checkpoint that triggers cell death during pachytene (Mahadevaiah et al 2008). This synapsis checkpoint is caused by asynapsed chromosomes sequestering the transcriptional silencing machinery away from the heterologous sex chromosomes, causing defective meiotic sex chromosome inactivation (MSCI) and inappropriate expression of sex chromosome-encoded gene products (Burgoyne et al 2009).
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