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Convergent genes shape budding yeast pericentromeres

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Original languageEnglish
JournalNature
DOIs
Publication statusPublished - 29 Apr 2020

Abstract

The 3D architecture of the genome governs its maintenance, expression and transmission. The cohesin complex organises the genome by topologically linking distant loci and is highly enriched in specialized chromosomal domains surrounding centromeres, called pericentromeres1-6. Here we report the 3D structure of budding yeast pericentromeres and establish the relationship between genome organisation and function. We find that convergent genes mark pericentromere borders and, together with core centromeres, define their structure and function by positioning cohesin. Centromeres load cohesin and convergent genes at pericentromere borders trap it. Each side of the pericentromere is organised into a looped conformation, with border convergent genes at the base. Microtubule attachment extends a single pericentromere loop, size-limited by convergent genes at its borders. Re-orienting genes at borders into a tandem configuration repositions cohesin, enlarges the pericentromere and impairs chromosome biorientation in mitosis. Thus, the linear arrangement of transcriptional units together with targeted cohesin loading shapes pericentromeres into a structure competent for chromosome segregation. Our results reveal the architecture of the chromosomal region within which kinetochores are embedded and the re-structuring caused by microtubule attachment. Furthermore, we establish a direct, causal relationship between 3D genome organization of a specific chromosomal domain and cellular function.

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