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10.1186/s12864-016-2516-6

http://scihub22266oqcxt.onion/10.1186/s12864-016-2516-6
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suck abstract from ncbi


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pmid27004515      BMC+Genomics 2016 ; 17 (ä): ä
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  • CTCF-mediated chromatin loops enclose inducible gene regulatory domains #MMPMID27004515
  • Oti M; Falck J; Huynen MA; Zhou H
  • BMC Genomics 2016[]; 17 (ä): ä PMID27004515show ga
  • Background: The CCTC-binding factor (CTCF) protein is involved in genome organization, including mediating three-dimensional chromatin interactions. Human patient lymphocytes with mutations in a single copy of the CTCF gene have reduced expression of enhancer-associated genes involved in response to stimuli. We hypothesize that CTCF interactions stabilize enhancer-promoter chromatin interaction domains, facilitating increased expression of genes in response to stimuli. Here we systematically investigate this model using computational analyses. Results: We use CTCF ChIA-PET data from the ENCODE project to show that CTCF-associated chromatin loops have a tendency to enclose regions of enhancer-regulated stimulus responsive genes, insulating them from neighboring regions of constitutively expressed housekeeping genes. To facilitate cell type-specific CTCF loop identification, we develop an algorithm to predict CTCF loops from ChIP-seq data alone by exploiting the CTCF motif directionality in loop anchors. We apply this algorithm to a hundred ENCODE cell line datasets, confirming the universality of our observations as well as identifying a general distinction between primary and immortal cells in loop-enclosed gene content. Finally, we combine the existing evidence to propose a model for the formation of CTCF loops in which partner sites are brought together by chromatin template reeling through stationary RNA polymerases, consistent with the transcription factory hypothesis. Conclusions: We provide computational evidence that CTCF-mediated chromatin interactions enclose domains of stimulus responsive enhancer-regulated genes, insulating them from nearby housekeeping genes. Electronic supplementary material: The online version of this article (doi:10.1186/s12864-016-2516-6) contains supplementary material, which is available to authorized users.
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