A simple model explains the cell cycle-dependent assembly of centromeric nucleosomes in holocentric species

Abstract

Centromeres are essential for chromosome movement. In independent taxa, species with holocentric chromosomes exist. In contrast to monocentric species, where no obvious dispersion of centromeres occurs during interphase, the organization of holocentromeres differs between condensed and decondensed chromosomes. During interphase, centromeres are dispersed into a large number of CENH3-positive nucleosome clusters in a number of holocentric species. With the onset of chromosome condensation, the centromeric nucleosomes join and form line-like holocentromeres. Using polymer simulations, we propose a mechanism relying on the interaction between centromeric nucleosomes and structural maintenance of chromosomes (SMC) proteins. Different sets of molecular dynamic simulations were evaluated by testing four parameters: (i) the concentration of Loop Extruders (LEs) corresponding to SMCs, (ii) the distribution and number of centromeric nucleosomes, (iii) the effect of centromeric nucleosomes on interacting LEs and (iv) the assembly of kinetochores bound to centromeric nucleosomes. We observed the formation of a line-like holocentromere, due to the aggregation of the centromeric nucleosomes when the chromosome was compacted into loops. A groove-like holocentromere structure formed after a kinetochore complex was simulated along the centromeric line. Similar mechanisms may also organize a monocentric chromosome constriction, and its regulation may cause different centromere types during evolution.

Holocentromeres can consist of merely a few megabase-sized satellite arrays

“…We asked how is the formation of a holocentric chromosome structure possible if each chromatid contains only a few megabase-scale centromere units? In a previously proposed holocentric model 7 , the interaction between centromere units and structural maintenance of chromosomes (SMC) proteins is essential during the process of chromosome condensation. Thousands of small centromere units were spread over the genome, resembling the observed distribution of centromere units in R. pubera 17 .…”

“…Thousands of small centromere units were spread over the genome, resembling the observed distribution of centromere units in R. pubera 17 . To form a metaphase holocentromere, short chromatin loops between each centromere unit, which anchored SMC proteins, brought them together into a line 7 .…”

Repeat-based holocentromeres influence genome architecture and karyotype evolution

“…This specific spacing might point to a selection mechanism for establishing centromere units separated by an optimal spacing required to fold the chromatin during cell-cycle progression and for the recruitment of CENH3-positive nucleosomes to build the line-like holocentromere at metaphase (Figure 7B). In silico modeling based on polymer simulations of chromatin folding in holocentric chromosomes suggests that centromere units can act as anchors of loop extruders, facilitating the formation of line-like holocentromeres during chromosome condensation (Ca ˆmara et al, 2021).…”

Consistencies and contradictions in different polymer models of chromatin architecture

“…They are regulated by the presence of other chromatin-bound factors. Such models successfully explained the existence of Topological Associating Domains and the compaction of different metaphase conformations by the presence of boundary elements halting the action of LEFs [42] , [43] , [44] , [45] . Loop extrusion was also observed to lead to optimal brush structures [33] , perhaps in similar ways as the growing preparation strategy of grafting polymers from surfaces that leads to higher concentration of grafted polymers [32] .…”