Abstract
During mitosis chromosomes reorganise into highly compact, rod-shaped forms, thought to consist of consecutive chromatin loops around a central protein scaffold. Condensin complexes are involved in chromatin compaction, but the contribution of other chromatin proteins, DNA sequence and histone modifications is less understood. A large region of fission yeast DNA inserted into a mouse chromosome was previously observed to adopt a mitotic organisation distinct from that of surrounding mouse DNA. Here, we show that a similar distinct structure is common to a large subset of insertion events in both mouse and human cells and is coincident with the presence of high levels of heterochromatic H3 lysine nine trimethylation (H3K9me3). Hi-C and microscopy indicate that the heterochromatinised fission yeast DNA is organised into smaller chromatin loops than flanking euchromatic mouse chromatin. We conclude that heterochromatin alters chromatin loop size, thus contributing to the distinct appearance of heterochromatin on mitotic chromosomes.
Highlights
During mitosis, chromatin is dramatically reorganised and compacted to form individual rod-shaped mitotic chromosomes that allow for proper segregation of the genetic material (Belmont, 2006)
To avoid any bias that might result from difference in base composition propidium iodide (PI) staining was used for all DNA intensity measurements rather DAPI, which preferentially binds to AT-rich DNA
Current models of mitotic chromosome organisation propose that the chromatin fibre is organised into consecutive loop arrays organised around a central scaffold as originally suggested by observations of extracted chromosomes (Paulson and Laemmli, 1977; Adolph et al, 1977; Earnshaw and Laemmli, 1983). These models are in part based upon Hi-C data which shows that in mitosis mammalian cells lose all Topologically Associating Domain (TAD) structures and chromosome compartments and show a uniform interaction pattern consisting of strong interactions along the diagonal that undergo a sharp drop-off over a longer range
Summary
Chromatin is dramatically reorganised and compacted to form individual rod-shaped mitotic chromosomes that allow for proper segregation of the genetic material (Belmont, 2006). A leading model for mitotic chromosome compaction proposes that chromatin is organised into loops that radiate out from a core scaffold composed of these key organising complexes (Maeshima and Eltsov, 2008). To a lesser extent telomeres, appear as visually distinct regions of constriction (Belmont, 2006) Studies in both yeast and vertebrates have found that condensin is enriched over these regions (Wang et al, 2005; D’Ambrosio et al, 2008, Kim et al, 2013), potentially explaining these structures as a local alteration in the loop structure. We propose a model whereby elevated condensin association with heterochromatin organises the underlying chromatin into arrays of loops that are smaller than those of surrounding non-heterochromatin regions, explaining the observed localised alteration of mitotic chromosome structure
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