The Impact of Centromeres on Spatial Genome Architecture

Abstract

The development of new technologies and experimental techniques is enabling researchers to see what was once unable to be seen. For example, the centromere was first seen as the mediator between spindle fiber and chromosome during mitosis and meiosis. Although this continues to be its most prominent role, we now know that the centromere functions beyond cellular division with important roles in genome organization and chromatin regulation. Here we aim to share the structures and functions of centromeres in various organisms beginning with the diversity of their DNA sequence anatomies. We zoom out to describe their position in the nucleus and ultimately detail the different ways they contribute to genome organization and regulation at the spatial level. Centromeres: Beyond Chromosome Segregation Eukaryotic genomes are not randomly organized. Chromatin is organized into multiple domains juxtaposed one after the other along the length of a chromosome and positioned into particular layouts and in particular regions of the nuclear space [1,2]. Among these chromatin domains, centromeres are universal to all eukaryotic chromosomes. First cytologically described in 1882 by Walther Flemming as the primary constrictions on condensed chromosomes attaching to spindle fibers [3], centromeres are essential for cell division by ensuring the equal partitioning of DNA into daughter cells. Highlights Centromeres' primary role is to ensure chromosome segregation. In addition to this well-known function, centromeres also have an impact on genome architecture. Microscopy studies have shown a propensity of centromere to cluster in many organisms. In addition, these clusters are not randomly localized in the nuclear space and tend to be found close to the nuclear periphery or around the nucleolus. At a large scale, chromosome architecture is constrained by centromeric interactions and the position of the centromere along each chromosome. Chromosome conformation capture experiments confirmed centromere clustering while shedding light onto unexpected consequences for genome spatial regulation: centromeres act as strong topological barriers preventing specific types of contacts between the two chromosomal arms.

High-quality chromosome-level genomes of two tilapia species reveal their evolution of repeat sequences and sex chromosomes

“…As expected, we found the locations of putative centromeres are colocalized with the junctions between the two arms of large intrachromosomal interaction domains ( Supplementary Fig. S4, Supplementary Table S3 ), similar to what has been reported in other vertebrates [39]. The monomer sequence of SATA satellites shows high degrees of variations (indels or SNPs) at certain monomer positions between copies of the same or different chromosomes, but there are intriguingly no variations at all in the last 58bp region across all the mapped loci of the two species ( Supplementary Fig.…”

High contiguity long read assembly ofBrassica nigraallows localization of active centromeres and provides insights into the ancestralBrassicagenome

“…However, all additional sites coincided with hypo-methylation suggesting functionality of the regions. This could imply potential scaffolding errors remaining in the dense repeat regions, although interestingly even though the data was more limiting the same pattern appeared to be apparent for the CN115125 genotype, which could suggest a dispersed structure for the active centromeric region 47 . Where comparison was feasible the two genotypes showed a common dichotomy of centromeric regions, with conservation of gene content but rapid divergence in sequence constitution driven by changes in retrotransposon composition.…”

Centromere evolution in the fungal genusVerticillium

“…Centromeres in fungi, plants, and animals co-localize within the nucleus (15,(51)(52)(53)(54)(55)58), a phenomenon that can be exploited for their identification (51, 52). Here, we used Hi-C to first establish chromosome-level genome assemblies and subsequently identify centromeres in every Verticillium species, and we demonstrate that centromere locations are in agreement with CenH3binding.…”