Cohesin-dependent globules and heterochromatin shape 3D genome architecture in S. pombe
Authors
Mizuguchi, TakeshiFudenberg, Geoffrey
Mehta, Sameet
Belton, Jon-Matthew
Taneja, Nitika
Folco, Hernan Diego
FitzGerald, Peter
Dekker, Job
Mirny, Leonid
Barrowman, Jemima
Grewal, Shiv I. S.
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyProgram in Systems Biology
Document Type
Journal ArticlePublication Date
2014-12-18Keywords
Cell Cycle ProteinsChromosomal Proteins, Non-Histone
*Genome, Fungal
Heterochromatin
Molecular Conformation
Schizosaccharomyces
Schizosaccharomyces pombe Proteins
Centromeres
Nuclear organization
Chromatin
Computational Biology
Genomics
Structural Biology
Systems Biology
Metadata
Show full item recordAbstract
Eukaryotic genomes are folded into three-dimensional structures, such as self-associating topological domains, the borders of which are enriched in cohesin and CCCTC-binding factor (CTCF) required for long-range interactions. How local chromatin interactions govern higher-order folding of chromatin fibres and the function of cohesin in this process remain poorly understood. Here we perform genome-wide chromatin conformation capture (Hi-C) analysis to explore the high-resolution organization of the Schizosaccharomyces pombe genome, which despite its small size exhibits fundamental features found in other eukaryotes. Our analyses of wild-type and mutant strains reveal key elements of chromosome architecture and genome organization. On chromosome arms, small regions of chromatin locally interact to form 'globules'. This feature requires a function of cohesin distinct from its role in sister chromatid cohesion. Cohesin is enriched at globule boundaries and its loss causes disruption of local globule structures and global chromosome territories. By contrast, heterochromatin, which loads cohesin at specific sites including pericentromeric and subtelomeric domains, is dispensable for globule formation but nevertheless affects genome organization. We show that heterochromatin mediates chromatin fibre compaction at centromeres and promotes prominent inter-arm interactions within centromere-proximal regions, providing structural constraints crucial for proper genome organization. Loss of heterochromatin relaxes constraints on chromosomes, causing an increase in intra- and inter-chromosomal interactions. Together, our analyses uncover fundamental genome folding principles that drive higher-order chromosome organization crucial for coordinating nuclear functions.Source
Nature. 2014 Dec 18;516(7531):432-5. doi: 10.1038/nature13833. Epub 2014 Oct 12. Link to article on publisher's siteDOI
10.1038/nature13833Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49933PubMed ID
25307058Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/nature13833