The roles of transcription, chromatin organisation and chromosomal processes in holocentromere establishment and maintenance

The centromere is a unique functional region on each eukaryotic chromosome where the kinetochore assembles and orchestrates microtubule attachment and chromosome segregation. Unlike monocentromeres that occupy a specific region on the chromosome, holocentromeres are diffused along the length of the chromosome. Despite being less common, holocentromeres have been verified in almost 800 nematode, insect, and plant species. Understanding of the molecular and epigenetic regulation of holocentromeres is lagging that of monocentromeres. Here we review how permissive locations for holocentromeres are determined across the genome, potentially by chromatin organisation, transcription, and non-coding RNAs, specifically in the nematode C. elegans. In addition, we discuss how holocentric CENP-A or CENP-T-containing nucleosomes are recruited and deposited, through the help of histone chaperones, licensing factors, and condensin complexes, both during de novo holocentromere establishment, and in each mitotic cell cycle. The process of resolving sister centromeres after DNA replication in holocentric organisms is also mentioned. Conservation and diversity between holocentric and monocentric organisms are highlighted, and outstanding questions are proposed.