Publication Date:
2009-05-22
Description:
Cohesin-mediated sister chromatid cohesion is essential for chromosome segregation and post-replicative DNA repair. In addition, evidence from model organisms and from human genetics suggests that cohesin is involved in the control of gene expression. This non-canonical role has recently been rationalized by the findings that mammalian cohesin complexes are recruited to a subset of DNase I hypersensitive sites and to conserved noncoding sequences by the DNA-binding protein CTCF. CTCF functions at insulators (which control interactions between enhancers and promoters) and at boundary elements (which demarcate regions of distinct chromatin structure), and cohesin contributes to its enhancer-blocking activity. The underlying mechanisms remain unknown, and the full spectrum of cohesin functions remains to be determined. Here we show that cohesin forms the topological and mechanistic basis for cell-type-specific long-range chromosomal interactions in cis at the developmentally regulated cytokine locus IFNG. Hence, the ability of cohesin to constrain chromosome topology is used not only for the purpose of sister chromatid cohesion, but also to dynamically define the spatial conformation of specific loci. This new aspect of cohesin function is probably important for normal development and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869028/" 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/PMC2869028/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hadjur, Suzana -- Williams, Luke M -- Ryan, Natalie K -- Cobb, Bradley S -- Sexton, Tom -- Fraser, Peter -- Fisher, Amanda G -- Merkenschlager, Matthias -- G0900491/Medical Research Council/United Kingdom -- G117/530/Medical Research Council/United Kingdom -- MC_U120027516/Medical Research Council/United Kingdom -- U.1200(U.1200)/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2009 Jul 16;460(7253):410-3. doi: 10.1038/nature08079. Epub 2009 May 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19458616" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
CD4-Positive T-Lymphocytes/metabolism
;
Cell Cycle Proteins/*metabolism
;
Cell Line
;
Chromosomal Proteins, Non-Histone/*metabolism
;
Chromosomes/*genetics/*metabolism
;
*Gene Expression Regulation, Developmental
;
Histones/metabolism
;
Humans
;
Interferon-gamma/*genetics
;
Mice
;
Nuclear Proteins/genetics/metabolism
;
Organ Specificity
;
Phosphoproteins/genetics/metabolism
;
Repressor Proteins/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
