Abstract
BackgroundA complex interplay between chromatin and topological machineries is critical for genome architecture and function. However, little is known about these reciprocal interactions, even for cohesin, despite its multiple roles in DNA metabolism.ResultsWe have used genome-wide analyses to address how cohesins and chromatin structure impact each other in yeast. Cohesin inactivation in scc1-73 mutants during the S and G2 phases causes specific changes in chromatin structure that preferentially take place at promoters; these changes include a significant increase in the occupancy of the − 1 and + 1 nucleosomes. In addition, cohesins play a major role in transcription regulation that is associated with specific promoter chromatin architecture. In scc1-73 cells, downregulated genes are enriched in promoters with short or no nucleosome-free region (NFR) and a fragile “nucleosome − 1/RSC complex” particle. These results, together with a preferential increase in the occupancy of nucleosome − 1 of these genes, suggest that cohesins promote transcription activation by helping RSC to form the NFR. In sharp contrast, the scc1-73 upregulated genes are enriched in promoters with an “open” chromatin structure and are mostly at cohesin-enriched regions, suggesting that a local accumulation of cohesins might help to inhibit transcription. On the other hand, a dramatic loss of chromatin integrity by histone depletion during DNA replication has a moderate effect on the accumulation and distribution of cohesin peaks along the genome.ConclusionsOur analyses of the interplay between chromatin integrity and cohesin activity suggest that cohesins play a major role in transcription regulation, which is associated with specific chromatin architecture and cohesin-mediated nucleosome alterations of the regulated promoters. In contrast, chromatin integrity plays only a minor role in the binding and distribution of cohesins.
Highlights
A complex interplay between chromatin and topological machineries is critical for genome architec‐ ture and function
Cohesins contribute to structuring chromatin To analyze what impact, if any, cohesins have on chromatin structure, we performed high-throughput sequencing of MNaseI-digested chromatin (MNase-seq) followed by dynamic analysis of nucleosome position and occupancy by sequencing (DANPOS) [35]
Cohesins contribute to structuring chromatin Here we provide evidence that cohesins help to determine the primary chromatin structure of specific DNA regions
Summary
A complex interplay between chromatin and topological machineries is critical for genome architec‐ ture and function. Cohesins are loaded at chromatin by the cohesin loader complex Scc2/Scc during G1 and early S phase in a non-stable conformation that promotes topological and non-topological interactions (depending on whether or not cohesin entraps chromosomal DNA inside its ring) through dynamic turnover [8,9,10]. The chromatin remodeling complex RSC recruits Scc2/Scc to specific promoters, where the cohesin loader helps to maintain the nucleosome-free region (NFR) for transcription activation [26]. Cohesins and cohesin loaders accumulate at non-overlapping peaks along the genome after their loading [12] It is unclear whether or not cohesins take part in chromatin remodeling and/or transcription in yeast
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