Contrasting behavior of heterochromatic and euchromatic chromosome portions and pericentric genome separation in pre-bouquet spermatocytes of hybrid mice.

Harry Scherthan,Karina Schöfisch,Thomas Dell,Doris Illner

doi:10.1007/s00412-014-0479-4

Abstract

The spatial distribution of parental genomes has attracted much interest because intranuclear chromosome distribution can modulate the transcriptome of cells and influence the efficacy of meiotic homologue pairing. Pairing of parental chromosomes is imperative to sexual reproduction as it translates into homologue segregation and genome haploidization to counteract the genome doubling at fertilization. Differential FISH tagging of parental pericentromeric genome portions and specific painting of euchromatic chromosome arms in Mus musculus (MMU) × Mus spretus (MSP) hybrid spermatogenesis disclosed a phase of homotypic non-homologous pericentromere clustering that led to parental pericentric genome separation from the pre-leptoteneup to zygotene stages. Preferential clustering of MMU pericentromeres correlated with particular enrichment of epigenetic marks (H3K9me3), HP1-γ and structural maintenance of chromosomes SMC6 complex proteins at the MMU major satellite DNA repeats. In contrast to the separation of heterochromatic pericentric genome portions, the euchromatic arms of homeologous chromosomes showed considerable presynaptic pairing already during leptotene stage of all mice investigated. Pericentric genome separation was eventually disbanded by telomere clustering that concentrated both parental pericentric genome portions in a limited nuclear sector of the bouquet nucleus. Our data disclose the differential behavior of pericentromeric heterochromatin and the euchromatic portions of the parental genomes during homologue search. Homotypic pericentromere clustering early in prophase I may contribute to the exclusion of large repetitive DNA domains from homology search, while the telomere bouquet congregates and registers spatially separated portions of the genome to fuel synapsis initiation and high levels of homologue pairing, thus contributing to the fidelity of meiosis and reproduction.Electronic supplementary materialThe online version of this article (doi:10.1007/s00412-014-0479-4) contains supplementary material, which is available to authorized users.

Highlights

Pairing of homologous chromosomes during meiosis is essential to fertility as it allows parental chromosomes to segregate and to generate haploid gametes or spores
Pericentromeric heterochromatin (PCH) regions have been observed to undergo a dynamic higher order clustering leading to the formation of a few large chromocenters during leptotene and zygotene stages (Scherthan et al 1996; Takada et al 2011), with the number of pericentromeric heterochromatin (PCH) clusters being well below the diploid number of mouse centromeres (2n=40), suggesting the unspecific bundling of proximal chromosome ends prior to synapsis initiation
During the preleptotene and leptotene stages, there were in average 7 and 6 large major sat FISH signal clusters/cell in Mus musculus (MMU) spermatocytes, respectively, while 11 large minor sat FISH clusters per pre/leptotene nucleus were noted in Mus spretus (MSP) spermatocytes (Fig. 1a, b)

Summary

Introduction

Pairing of homologous chromosomes during meiosis is essential to fertility as it allows parental chromosomes to segregate and to generate haploid gametes or spores. Centromere coupling seems to install a premeiotic nuclear architecture that sets an early stage for the meiotic pairing dance (Moore and Shaw 2009; Richards et al 2012). These observations imply a differential behavior of centromeric/pericentromeric and euchromatic genome portions during the onset of first meiotic prophase. Both the association of non-homologous centromeres and the formation of the telomere bouquet seem to direct the complex choreography of the homologue pairing process (Klutstein and Cooper 2014; Obeso et al 2014; Scherthan 2001)

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