Publication Date:
2014-10-14
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465753/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465753/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mizuguchi, Takeshi -- Fudenberg, Geoffrey -- Mehta, Sameet -- Belton, Jon-Matthew -- Taneja, Nitika -- Folco, Hernan Diego -- FitzGerald, Peter -- Dekker, Job -- Mirny, Leonid -- Barrowman, Jemima -- Grewal, Shiv I S -- HG003143/HG/NHGRI NIH HHS/ -- R01 HG003143/HG/NHGRI NIH HHS/ -- U54CA143874/CA/NCI NIH HHS/ -- Z01 BC010523-04/Intramural NIH HHS/ -- Z01 BC010523-05/Intramural NIH HHS/ -- ZIA BC010523-07/Intramural NIH HHS/ -- England -- Nature. 2014 Dec 18;516(7531):432-5. doi: 10.1038/nature13833. Epub 2014 Oct 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA [2]. ; 1] Graduate Program in Biophysics, Harvard University, Boston, Massachusetts 02115, USA [2] Institute for Medical Engineering and Sciences, Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [3]. ; Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Program in Systems Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. ; Genome Analysis Unit, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] Graduate Program in Biophysics, Harvard University, Boston, Massachusetts 02115, USA [2] Institute for Medical Engineering and Sciences, Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25307058" target="_blank"〉PubMed〈/a〉
Keywords:
Cell Cycle Proteins/*metabolism
;
Chromosomal Proteins, Non-Histone/*metabolism
;
*Genome, Fungal
;
Heterochromatin/*metabolism
;
Molecular Conformation
;
Schizosaccharomyces/genetics/*physiology
;
Schizosaccharomyces pombe Proteins/*metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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