The Rabl configuration limits topological entanglement of chromosomes in budding yeast

Abstract

The three dimensional organization of genomes remains mostly unknown due to their high degree of condensation. Biophysical studies predict that condensation promotes the topological entanglement of chromatin fibers and the inhibition of function. How organisms balance between functionally active genomes and a high degree of condensation remains to be determined. Here we hypothesize that the Rabl configuration, characterized by the attachment of centromeres and telomeres to the nuclear envelope, helps to reduce the topological entanglement of chromosomes. To test this hypothesis we developed a novel method to quantify chromosome entanglement complexity in 3D reconstructions obtained from Chromosome Conformation Capture (CCC) data. Applying this method to published data of the yeast genome, we show that computational models implementing the attachment of telomeres or centromeres alone are not sufficient to obtain the reduced entanglement complexity observed in 3D reconstructions. It is only when the centromeres and telomeres are attached to the nuclear envelope (i.e. the Rabl configuration) that the complexity of entanglement of the genome is comparable to that of the 3D reconstructions. We therefore suggest that the Rabl configuration is an essential player in the simplification of the entanglement of chromatin fibers.

Interplay of the nuclear envelope with chromatin in physiology and pathology

“…In addition to chromosome segregation, centromere tethering at the NE mediates peri-centromeric heterochromatin and subsequent gene silencing, through molecular association with Lem2 as shown in fission yeast [37]. The advent of 3 C-based technologies showed that this attachment to the NE limits topological entanglement of the budding yeast genome and facilitates chromosome segregation [38]. Importantly, recent evidence shows that centromeres influence genome organization and chromosome architecture, especially in yeast [39].…”

The Easter Egg Weevil (Pachyrhynchus) genome reveals synteny in Coleoptera across 200 million years of evolution

“…Another architectural feature of Pachyrhynchus ’ genome above the chromosome level includes the Rabl-like configuration of chromosomes, where centromeres and telomeres cluster at opposite/different regions of the cell. These features are important to note because they may serve an important evolutionary function, such as reducing chromosomal entanglements during interphase as well as regulating chromosomal compartmentalization (Mizuguchi et al 2015, Pouokam et al 2019). Both major lineages of Diptera, the Nematocera (e.g.…”

Quantitative Study of the Chiral Organization of the Phage Genome Induced by the Packaging Motor

“…Each of the samples in the ensemble is derived from the original protein backbone by surrounding the protein backbone by a very large sphere and connecting the two ends of the protein to a point in this sphere through two straight lines. This approach was recently generalized to study the linking and entanglement complexity of chromosomes in budding yeast ( 90 ). Most recently, a new formalization of entanglement in open curves has been introduced through the concepts of knotoids ( 91 ) and knotting probability of an arc diagram ( 92 ); whether this will be the correct formulation for biological problems remains to be determined.…”