Developmental regulation of mitotic chromosome formation revealed by condensin reporter mice

Gillian Taylor, Lewis MacDonald, Jimi Wills, Matilda Bui, Lucy Scott, Ioannis Christodoulou, Dimitrios K Papadopoulos, Andrew J Wood

Research output: Contribution to journalArticle

Abstract

Germline mutations affecting subunits of condensins I and II cause tissue-specific disease in humans and mice through chromosome segregation failure. However, condensin activity is universally required for chromosome segregation, and hence the developmental basis for these phenotypes is not understood. Using novel transgenic mouse strains, we show that cell-lineage-specific dosage of non-SMC condensin subunits controls the number of catalytically active holocomplexes during different haematopoietic cell divisions in mice. Thymic T cell precursors load significantly higher levels of both condensin I and II subunits onto mitotic chromosomes compared to B cell or erythroid precursors, and undergo elevated mitotic chromosome compaction. Thymic T cells also experience relatively greater chromosome instability in a condensin II hypomorphic strain, indicating that genome propagation requires particularly high condensin activity at this stage of development. Our data highlight developmental changes in the mitotic chromosome condensation pathway, which could contribute to tissue-specific phenotypes in chromosome instability syndromes.
Original languageEnglish
JournalbioRxiv
DOIs
Publication statusPublished - 4 Nov 2020

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