Cohesins form chromosomal cis-interactions at the developmentally regulated IFNG locus

Title: Cohesins form chromosomal cis-interactions at the developmentally regulated IFNG locus
Authors: Hadjur, S
Williams, LM
Ryan, NK
Cobb, BS
Sexton, T
Fraser, P
Fisher, AG
Merkenschlager, M
Item Type: Journal Article
Abstract: Cohesin-mediated sister chromatid cohesion is essential for chromosome segregation and post-replicative DNA repair1,2. In addition, evidence from model organisms3,4,5,6 and from human genetics7 suggests that cohesin is involved in the control of gene expression8,9. 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 CTCF10,11,12,13. CTCF functions at insulators (which control interactions between enhancers and promoters) and at boundary elements (which demarcate regions of distinct chromatin structure)14, and cohesin contributes to its enhancer-blocking activity10,11. 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 cohesion1,2, but also to dynamically define the spatial conformation of specific loci. This new aspect of cohesin function is probably important for normal development3,4,5,6 and disease7.
Issue Date: 16-Jul-2009
Date of Acceptance: 27-Apr-2009
URI: http://hdl.handle.net/10044/1/71585
DOI: https://doi.org/10.1038/nature08079
ISSN: 0028-0836
Publisher: Nature Research
Start Page: 410
End Page: U130
Journal / Book Title: Nature
Volume: 460
Issue: 7253
Copyright Statement: © 2009 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1038/nature08079.
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: PO4050659629
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CCCTC-BINDING FACTOR
GENE-EXPRESSION
CELL DIFFERENTIATION
INTERFERON-GAMMA
CONTROL REGION
CTCF
TRANSCRIPTION
CHROMATIN
CONFORMATION
GENOME
Animals
CCCTC-Binding Factor
CD4-Positive T-Lymphocytes
Cell Cycle Proteins
Cell Line
Chromosomal Proteins, Non-Histone
Chromosomes
Gene Expression Regulation, Developmental
Histones
Humans
Interferon-gamma
Mice
Nuclear Proteins
Organ Specificity
Phosphoproteins
Repressor Proteins
CD4-Positive T-Lymphocytes
Cell Line
Chromosomes
Animals
Humans
Mice
Cell Cycle Proteins
Nuclear Proteins
Chromosomal Proteins, Non-Histone
Histones
Phosphoproteins
Repressor Proteins
Organ Specificity
Gene Expression Regulation, Developmental
Interferon-gamma
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CCCTC-BINDING FACTOR
GENE-EXPRESSION
CELL DIFFERENTIATION
INTERFERON-GAMMA
CONTROL REGION
CTCF
TRANSCRIPTION
CHROMATIN
CONFORMATION
GENOME
MD Multidisciplinary
General Science & Technology
Publication Status: Published
Online Publication Date: 2009-05-20
Appears in Collections:Clinical Sciences
Molecular Sciences



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