Allshire lab paper featured in eLife. Authors Image The analysis presented suggest that elevated condensin association with heterochromatin organises the underlying chromatin into arrays of loops that are smaller than those of surrounding non-heterochromatin regions, thus explaining the observed alterations in mitotic chromosome structure. Fitz-James, M.H., Tong, P., Pidoux, A.L., Ozadam, H., Yang, L., White, S.A., Dekker, J., and Allshire, R.C. Summary of Paper by Lori Koch DNA is packaged into chromosomes which are further compacted during the process of cell division. The condensin protein complexes are essential for chromosome structure however it is unknown whether chemical modifications of the histone proteins embedded in the DNA also contribute to compaction. To uncover determinants of chromosome structure, scientists in the Allshire group investigated a hybrid mouse cell line harbouring a large insertion of DNA from the fission yeast Schizosaccharomyces pombe. Previous research initiated in 1986 by group leader Robin Allshire when he was a post-doc had shown that the inserted DNA in this hybrid appeared more compacted (Cell 1987, J. Cell Sci 1994). In their recent study led by PhD student Max Fitz-James and published in eLife, the scientists used cutting-edge methods such as nanopore sequencing and Hi-C to investigate yeast-mammal hybrid chromosome structure. Immuno-localisation revealed an even distribution of condensin complex across the foreign DNA inserted in a mouse chromosome, despite a significant reduction in the level of DNA/chromatin across the same region. This observation suggested that more condensin is loaded across the inserted foreign DNA but the reason for this was unclear. The team constructed several new cell lines harbouring S. pombe DNA in host chromosomes, several of which showed a similar compacted appearance to that of the original insertion in a mouse chromosome. Interestingly, they detected high levels of histone 3 lysine 9 tri-methylation (H3K9me3) across such insertions, which is a chemical modification associated with a denser structure called heterochromatin. Tracing the contacts between different stretches of DNA using Hi-C showed that the inserted S. pombe DNA formed shorter chromatin loops. Overall, their results suggest that heterochromatin formation can alter mitotic chromosome structure by stimulating condensin loading, resulting in a greater number of shorter loops per unit length. Related links Journal Link Allshire Lab Website DOI This article was published on 2024-06-17
