Chromosomal rearrangement interferes with meiotic X chromosome inactivation

Abstract

Heterozygosity for certain mouse and human chromosomal rearrangements is characterized by the incomplete meiotic synapsis of rearranged chromosomes, by their colocalization with the XY body in primary spermatocytes, and by male-limited sterility. Previously, we argued that such X-autosomal associations could interfere with meiotic sex chromosome inactivation. Recently, supporting evidence has reported modifications of histones in rearranged chromosomes by a process called the meiotic silencing of unsynapsed chromatin (MSUC). Here, we report on the transcriptional down-regulation of genes within the unsynapsed region of the rearranged mouse chromosome 17, and on the subsequent disturbance of X chromosome inactivation. The partial transcriptional suppression of genes in the unsynapsed chromatin was most prominent prior to the mid-pachytene stage of primary spermatocytes. Later, during the mid-late pachytene, the rearranged autosomes colocalized with the XY body, and the X chromosome failed to undergo proper transcriptional silencing. Our findings provide direct evidence on the MSUC acting at the mRNA level, and implicate that autosomal asynapsis in meiosis may cause male sterility by interfering with meiotic sex chromosome inactivation.[Supplemental material is available online at www.genome.org. The microarray data have been submitted to NCBI/GEO under accession no. GSE7306.]Sex chromosomes exhibit unique behavior during the first meiotic prophase of spermatogenesis. Because they lack a homologous pairing partner, except for a tiny pseudoautosomal region Previously, we proposed a possible link between the incomplete synapsis of chromosomes involved in male-sterile autosomal rearrangements and X chromosome inactivation in male meiosis (Forejt 1982;Forejt 1996). Here we investigated the phenomenon by analyzing both the aberrant chromosome synapsis with BRCA1 and gamma H2AX markers, and the global transcriptome changes with microarrays. Our studies revealed a significant transcriptional down-regulation of genes in the unsynapsed autosomal chromatin in pre-mid-pachytene spermatocytes that was followed by a partial breakdown of transcriptional silencing of the X chromosome during the mid-late-pachytene stage. Results Meiotic effects of T(16;17)43H translocationTo assess the meiotic effects of a male-sterile chromosomal rearrangement, we developed the C57BL/10-T43H/T43H congenic strain (hereafter B10-T43/T43) that carries the autosomal reciprocal translocation T(16;17)43H (hereafter T43) on the genetic background of the C57BL/10ScScPh (abbreviated B10) inbred strain. Consequently, by comparing B10-T43/T43, B10-T43/+, and B10-+/+ males, we could distinguish a possible position effect of the translocation break from the effect of asynapsis on the identical genetic background.Only B10-T43/+ heterozygotes were completely sterile and displayed an incomplete synapsis of the translocation quadrivalent at the pachytene. The B10-T43/T43 translocation homozygotes and B10 males without translocation were fertile, had no pairing d...

A Complex Genetic Basis to X-Linked Hybrid Male Sterility Between Two Species of House Mice

“…Disrupted genomic imprinting has been put forth as a general mechanism for asymmetric isolation in mammals (Vrana 2007) and stands as a formal possibility for X-linked sterility in house mice (Storchová et al 2004;Homolka et al 2007). Likewise, expression divergence between M. musculus and M. domesticus of specific Xlinked loci could also be involved in the disruption of spermatogenesis in hybrids.…”

Did sex chromosome turnover promote divergence of the major mammal groups?

“…Individuals heterozygous for translocation produce half balanced and half unbalanced gametes, a severe reproductive barrier between old and new systems. Interference with the dosage compensation system appears to contribute to infertility in mouse translocation hybrids 70.…”

Sexual dimorphism in prophase I of meiosis in the Northern mole vole (Ellobius talpinus Pallas, 1770) with isomorphic (XX) chromosomes in males and females

“…According to literature data, the formation of a sex body, which gradually moves into the nucleus periphery in prophase I of meiosis, is considered to be characteristic of mammalian males with heteromorphic XY sex chromosomes. In E. tancrei as in E. talpinus, XX chromosomes are isomorphic in the pattern of G-banding in females and males, and a sex body is also formed in representatives of these species (Bogdanov et al, 1986) Moreover, the sex bivalent of E. talpinus is surrounded with an electron-dense cloud, which is a morphological feature of silencing of sex chromosome genes of males (Homolka et al, 2007). In contrast to males, the behaviour and SC structure of the sex bivalent SC in females are identical to those of autosomes.…”