Abstract
Chromosome compaction is essential for reliable transmission of genetic information. Experiments suggest that ∼1000-fold compaction is driven by condensin complexes that extrude chromatin loops, by progressively collecting chromatin fiber from one or both sides of the complex to form a growing loop. Theory indicates that symmetric two-sided loop extrusion can achieve such compaction, but recent single-molecule studies (Golfier et al., 2020) observed diverse dynamics of condensins that perform one-sided, symmetric two-sided, and asymmetric two-sided extrusion. We use simulations and theory to determine how these molecular properties lead to chromosome compaction. High compaction can be achieved if even a small fraction of condensins have two essential properties: a long residence time and the ability to perform two-sided (not necessarily symmetric) extrusion. In mixtures of condensins I and II, coupling two-sided extrusion and stable chromatin binding by condensin II promotes compaction. These results provide missing connections between single-molecule observations and chromosome-scale organization.
Highlights
During mitosis in metazoan cells, each chromosome is linearly compacted ~1000-fold from a ~1-mmlong chromatin polymer globule into a ~1 mm array of chromatin loops (Paulson and Laemmli, 1977; Marsden and Laemmli, 1979; Earnshaw and Laemmli, 1983; Maeshima et al, 2005)
We investigated whether asymmetric two-sided extrusion or a mixture of one- and two-sided loop-extruding factors (LEFs) with different dynamics can generate the high degree of linear compaction observed for mitotic chromosomes in vivo
Based on the idea of closing gaps between LEFs, we previously argued that asymmetric two-sided extrusion could fully linearly compact mitotic chromosomes provided that the residence time is sufficiently long; in particular, we require lslow=d ) 1(Banigan and Mirny, 2019; Figure 1b)
Summary
During mitosis in metazoan cells, each chromosome is linearly compacted ~1000-fold from a ~1-mmlong chromatin polymer globule into a ~1 mm array of chromatin loops (Paulson and Laemmli, 1977; Marsden and Laemmli, 1979; Earnshaw and Laemmli, 1983; Maeshima et al, 2005) This remarkable reorganization is primarily driven by the protein complex condensin (Hirano and Mitchison, 1994; Saitoh et al, 1994; Saka et al, 1994; Strunnikov et al, 1995; Hirano et al, 1997; Shintomi et al, 2015; Gibcus et al, 2018), which is one of a class of DNA-binding complexes known as structural maintenance of chromosomes (SMC) complexes. It has not been established how condensins with the properties observed in vitro can attain the high degree of linear compaction required for mitotic chromosome compaction in vivo
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