Centromere positioning orchestrates telomere bouquet formation and the initiation of meiotic differentiation

Accurate gametogenesis requires the establishment of the telomere bouquet, an evolutionarily conserved, 3D chromosomal arrangement. In this spatial configuration, telomeres temporarily aggregate at the nuclear envelope during meiotic prophase, which facilitates chromosome pairing and recombination. The mechanisms governing the assembly of the telomere bouquet remain largely unexplored, primarily due to the challenges in visualizing and manipulating the bouquet. Here, using Schizosaccharomyces pombe as a model system to elucidate telomere bouquet function, we reveal that centromeres, traditionally perceived as playing a passive role in the chromosomal reorganization necessary for bouquet assembly, likely serve as the key initiators of telomere bouquet formation. We demonstrate that centromeres have the remarkable capability to induce telomere mobilization, which is even sufficient to trigger bouquet formation and the meiotic transcription program in mitotic cells. This discovery highlights the finely tuned control exerted over long-distance heterochromatic regions and underscores a pivotal step in the mechanism of eukaryotic telomere bouquet formation. In order to assess the effect of centromere declustering on general gene expression, we performed RNA-seq of asynchronic log-phase cultures in rich medium of cells of wt and sad1.2 csi1Δ backgrounds.