Little is known about how distance between homologous chromosomes are controlled during the cell cycle. Here, we show that the distribution of centromere components display two discrete clusters placed to either side of the centrosome and apical/basal axis from prophase to G1 interphase. 4-Dimensional live cell imaging analysis of centromere and centrosome tracking reveals that centromeres oscillate largely within one cluster, but do not cross over to the other cluster. We propose a model of an axis-dependent ipsilateral restriction of chromosome oscillations throughout mitosis.

Meiosis involves deep changes in the spatial organisation and interactions of chromosomes enabling the two primary functions of this process: increasing genetic diversity and reducing ploidy level. These two functions are ensured by crucial events such as homologous chromosomal pairing, synapsis, recombination and segregation. In most sexually reproducing eukaryotes, homologous chromosome pairing depends on a set of mechanisms, some of them associated with the repair of DNA double-strand breaks (DSBs) induced at the onset of prophase I, and others that operate before DSBs formation. In this article, we will review various strategies utilised by model organisms for DSB-independent pairing. Specifically, we will focus on mechanisms such as chromosome clustering, nuclear and chromosome movements, as well as the involvement of specific proteins, non-coding RNA, and DNA sequences.

Sexual reproduction and the specialized cell division it relies upon, meiosis, are biological processes that present an incredible degree of both evolutionary conservation and divergence. One clear example of this paradox is the role of the evolutionarily ancient PCH-2/HORMAD module during meiosis. On one hand, the complex, and sometimes disparate, meiotic defects observed when PCH-2 and/or the meiotic HORMADS are mutated in different model systems have prevented a straightforward characterization of their conserved functions. On the other hand, these functional variations demonstrate the impressive molecular rewiring that accompanies evolution of the meiotic processes these factors are involved in. While the defects observed in pch-2 mutants appear to vary in different systems, in this review, I argue that PCH-2 has a conserved meiotic function: to coordinate meiotic recombination with synapsis to ensure an appropriate number and distribution of crossovers. Further, given the dramatic variation in how the events of recombination and synapsis are themselves regulated in different model systems, the mechanistic differences in PCH-2 and meiotic HORMAD function make biological sense when viewed as species-specific elaborations layered onto this fundamental, conserved role.

Chromosome organization is highly dynamic and plays an essential role during cell function. It was recently found that pairs of the homologous chromosomes are continuously separated at mitosis and display a haploid (1n) chromosome set, or \"antipairing,\" organization in human cells. Here, we provide an introduction to the current knowledge of homologous antipairing in humans and its implications in human disease.

In most eukaryotes, pairing of homologous chromosomes is an essential feature of meiosis that ensures homologous recombination and segregation. However, when the pairing process begins, it is still under investigation. Contrasting data exists in Mus musculus, since both leptotene DSB-dependent and preleptotene DSB-independent mechanisms have been described. To unravel this contention, we examined homologous pairing in pre-meiotic and meiotic Mus musculus cells using a three-dimensional fluorescence in situ hybridization-based protocol, which enables the analysis of the entire karyotype using DNA painting probes. Our data establishes in an unambiguously manner that 73.83% of homologous chromosomes are already paired at premeiotic stages (spermatogonia-early preleptotene spermatocytes). The percentage of paired homologous chromosomes increases to 84.60% at mid-preleptotene-zygotene stage, reaching 100% at pachytene stage. Importantly, our results demonstrate a high percentage of homologous pairing observed before the onset of meiosis; this pairing does not occur randomly, as the percentage was higher than that observed in somatic cells (19.47%) and between nonhomologous chromosomes (41.1%). Finally, we have also observed that premeiotic homologous pairing is asynchronous and independent of the chromosome size, GC content, or presence of NOR regions.

Different DNA methylation patterns presented on different tissues or cell types are considered as one of the main reasons accounting for the tissue-specific gene expressions. In recent years, many methods have been proposed to identify differentially methylated regions (DMRs) based on the mixture of methylation signals from homologous chromosomes. To investigate the possible influence of homologous chromosomes on methylation analysis, this paper proposed a method (MHap) to construct methylation haplotypes for homologous chromosomes in CpG dense regions. Through comparing the methylation consistency between homologous chromosomes in different cell types, it can be found that majority of paired methylation haplotypes derived from homologous chromosomes are consistent, while a lower methylation consistency was observed in the breast cancer sample. It also can be observed that the hypomethylation consistency of differentiated cells is higher than that of the corresponding undifferentiated stem cells. Furthermore, based on the methylation haplotypes constructed on homologous chromosomes, a method (MHap_DMR) is developed to identify DMRs between differentiated cells and the corresponding undifferentiated stem cells, or between the breast cancer sample and the normal breast sample. Through comparing the methylation haplotype modes of DMRs in two cell types, the DNA methylation changing directions of homologous chromosomes in cell differentiation and cancerization can be revealed. The code is available at: https://github.com/xqpeng/MHap_DMR.

The three-dimensional (3D) organization of chromatin in the nucleus of diploid eukaryotic organisms has fascinated biologists for many years. Despite major progress in chromatin conformation studies, current knowledge regarding the spatial organization of diploid (maternal and paternal) genomes is still limited. Recent advances in Hi-C technology and data processing approaches have enabled construction of diploid Hi-C contact maps. These maps greatly accelerated the pace of novel discoveries in haplotype-resolved 3D genome studies, revealing the role of allele biased chromatin conformation in transcriptional regulation. Here, we review emerging concepts and haplotype phasing strategies of Hi-C data in 3D diploid genome studies. We discuss new insights on homologous chromosomal organization and the interplay between allelic biased chromatin architecture and several nuclear functions, explaining how haplotype-resolved Hi-C technologies have been used to resolve important biological questions.

Three-dimensional eukaryotic genome organization provides the structural basis for gene regulation. In Drosophila melanogaster, genome folding is characterized by somatic homolog pairing, where homologous chromosomes are intimately paired from end to end; however, how homologs identify one another and pair has remained mysterious. Recently, this process has been proposed to be driven by specifically interacting \'buttons\' encoded along chromosomes. Here, we turned this hypothesis into a quantitative biophysical model to demonstrate that a button-based mechanism can lead to chromosome-wide pairing. We tested our model using live-imaging measurements of chromosomal loci tagged with the MS2 and PP7 nascent RNA labeling systems. We show solid agreement between model predictions and experiments in the pairing dynamics of individual homologous loci. Our results strongly support a button-based mechanism of somatic homolog pairing in Drosophila and provide a theoretical framework for revealing the molecular identity and regulation of buttons.

Meiosis is a key event in the manufacturing of an oocyte. During this process, the oocyte creates a set of unique chromosomes by recombining paternal and maternal copies of homologous chromosomes, and by eliminating one set of chromosomes to become haploid. While meiosis is conserved among sexually reproducing eukaryotes, there is a bewildering diversity of strategies among species, and sometimes within sexes of the same species, to achieve proper segregation of chromosomes. Here, we review the very first steps of meiosis in females, when the maternal and paternal copies of each homologous chromosomes have to move, find each other and pair. We explore the similarities and differences observed in C. elegans, Drosophila, zebrafish and mouse females.

Polyploid organisms provide additional opportunities to study meiosis in a more complex context since more than two potential homologous chromosomes are available. When the chromosome complement of a diploid individual is duplicated, each chromosome is accompanied by one identical and two homologous chromosomes within the same nucleus. In this situation, a competition in pairing/synapsis/chiasma formation between identical and homologous (but not necessarily identical) chromosomes can occur. Several studies have been conducted in different species to address whether there are preferences in crossover formation between identical rather than homologous chromosomes. In this study, multivalent and chiasma frequencies were cytologically analyzed in synthetic autotetraploids of Arabidopsis thaliana including the accessions Col, Ler, and the Col/Ler hybrid. Fluorescence in situ hybridization was conducted to identify each chromosome at metaphase I. The new Col and Ler tetraploids showed high multivalent frequencies, exceeding the theoretical 66.66% expected on a simple random end-pairing model, thus indicating that there are more than two autonomous synaptic sites per chromosome despite their small size. However, a significant excess of bivalent pairs was found in the Col/Ler hybrid, mainly due to the contribution of chromosomes 2 and 3. The mean chiasma frequencies of the three artificial autotetraploids were about twofold the corresponding mean cell chiasma frequencies of their diploid counterparts. The relative contribution of each chromosome to the total chiasma frequency was similar in the three genotypes, with the exception of a lower contribution of chromosome 3 in the hybrid. Preferences for chiasma formation between identical and homologous chromosomes were analyzed in Col/Ler 4x, taking advantage of the cytological differences between the accessions: variations in the size of the 45S rDNA region on the short arm of chromosome 2 and changes in the size and localization of the 5S rDNA region in chromosome 3. We observed a different behavior of chromosomes 2 and 3, i.e., random chiasma formation between identical and homologous chromosomes 2, and preferences for chiasma formation between homologous chromosomes 3. Hence, our results reveal the existence of chromosome-specific mechanisms responsible for these preferences.