Fungi as models of centromere innovation: from DNA sequence to 3-dimensional arrangement

Faithful chromosome segregation is facilitated by the centromeres, specialized genomic loci, which connect chromosomes to microtubules in every cell cycle by recruiting the kinetochore complex. However, a single conserved code does not govern the formation and maintenance of centromeres, as we begin to realize that enormous diversity exists in molecular mechanisms dictating centromere homeostasis across species. The fungal kingdom is a vast resource to study and appreciate the divergent nature of the conserved phenomenon of chromosome segregation. Studies in the fungal kingdom enable researchers to view the evolution of centromeres at the molecular level. While some organisms, such as Saccharomyces cerevisiae, rely on a strict genetically determined centromere establishment, most fungi adopt epigenetically driven mechanisms of centromere propagation. This epigenomic regulation ranges from modifications on the underlying DNA to histones forming the centric and pericentric regions. The centromere DNA sequence, arrangement of sequence elements, its transcription state, and the replication timing, as well as its spatial position in the nucleus, play a major role in determining centromere stability and its function. In this review, we aim to highlight the spectrum of centromere regulatory mechanisms observed in fungi and discuss the gaps in the research that can provide new perspectives on centromere biology.