Nucleosome eviction in mitosis assists condensin loading and chromosome condensation

Abstract

Condensins associate with DNA and shape mitotic chromosomes. Condensins are enriched nearby highly expressed genes during mitosis, but how this binding is achieved and what features associated with transcription attract condensins remain unclear. Here, we report that condensin accumulates at or in the immediate vicinity of nucleosome-depleted regions during fission yeast mitosis. Two transcriptional coactivators, the Gcn5 histone acetyltransferase and the RSC chromatin-remodelling complex, bind to promoters adjoining condensin-binding sites and locally evict nucleosomes to facilitate condensin binding and allow efficient mitotic chromosome condensation. The function of Gcn5 is closely linked to condensin positioning, since neither the localization of topoisomerase II nor that of the cohesin loader Mis4 is altered in gcn5 mutant cells. We propose that nucleosomes act as a barrier for the initial binding of condensin and that nucleosome-depleted regions formed at highly expressed genes by transcriptional coactivators constitute access points into chromosomes where condensin binds free genomic DNA.

The human Cranio Facial Development Protein 1 (Cfdp1) gene encodes a protein required for the maintenance of higher-order chromatin organization

“…A recent study in fission yeast suggests that nucleosome eviction promotes condensin loading in mitosis35. This is interesting in view of the interaction we detected between CFDP1 and members of the SRCAP complex.…”

A conserved role of the RSC chromatin remodeler in the establishment of nucleosome-depleted regions

“…Nonetheless, the main phenotypes of the rsc1 mutant, and the snf21 - ts mutant for that matter, are cell elongation associated with chromosomes segregation defects. Although these phenotypes may result from the reduced expression of specific genes, a recent study rather points to a direct role of RSC and nucleosome eviction in condensin loading and chromosome condensation (Toselli-Mollereau et al 2016). A genetic screen for functional partners of condensin in fission yeast (synthetic lethality with cut3 - 477 that encodes a condensin ATPase subunit) identified alleles of arp9 and snf21 that both showed high frequency of chromatin bridges in anaphase (Robellet et al 2014).…”

A Sir2-regulated locus control region in the recombination enhancer ofSaccharomyces cerevisiaespecifies chromosome III structure

“…Perhaps condensin is attracted to such regions, which is consistent with the association of condensin with promoters of active genes in mitotic cells, where enrichment was greatest at unwound regions of DNA [45]. Furthermore, nucleosome eviction by transcriptional coactivators was found to assist condensin loading in yeast [46], though the mechanism of loading remains poorly understood. Recruitment of condensin to the RDT1 promoter LCR therefore provides an outstanding opportunity for dissecting mechanisms of condensin loading and function.…”