High Multiplex Translocation Sequencing Reveals the Versatile Role of Condensin II in Chromosomal Translocations

ABSTRACT: Chromosomal translocations play pivotal roles in various physiological and pathological processes, such as immunoglobulin production and tumor progression; however, the infrequency of chromosomal translocation events has impeded the exploration of the underlying mechanisms. To tackle this challenge, we devised a strategy to report and enrich cells with translocations in vitro, in conjunction with a novel method termed High Multiplex Translocation Sequencing (HMTS), to capture genome-wide translocations from multiple bait regions simultaneously. Analysis of HMTS data unveiled a preference for translocations to occur at Topologically Associating Domain (TAD) boundaries, and experimental disruption of the TAD boundary indeed led to a reduction in translocation frequency, exemplified by translocations involving ERG. Knockdown of Cohesin or condensin II was observed distinct roles in translocations. Cohesin deficiency promoted long-distance translocations, while condensin II deficiency promoted short distance translocation, inside TAD, and decreased intra-chromatin long-distance translocation, particularly at TAD boundaries. For inter-chromatin, although condensin II deficiency also decreased the translocation at TAD boundaries, and highly transcription regions while paradoxically slightly increased inter-chromatin translocation ratio, suggesting that condensin II physiologically mediated inter-chromatin interaction at TAD boundary regions but simultaneously restricted interaction from other regions, such as centromere. Our new translocation sequencing method revealed the versatile role of condensin II in controlling intra-chromatin short-distance, long-distance, and inter-chromosome translocations.

ORGANISM(S): Homo sapiens

PROVIDER: GSE268339 | GEO | 2024/05/31

REPOSITORIES: GEO