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CTCF Mediates Interchromosomal Colocalization Between Igf2/H19 and Wsb1/Nf1
Jian Qun Ling,1Tao Li,1Ji Fan Hu,1Thanh H. Vu,1Hui Ling Chen,1Xin Wen Qiu,1Athena M. Cherry,2Andrew R. Hoffman1*
Gene transcription may be regulated by remote enhancer or insulatorregions through chromosome looping. Using a modification ofchromosome conformation capture (3C) and fluorescence in situhybridization, we found that one allele of the insulin-likegrowth factor 2 (Igf2)/H19 imprinting control region (ICR) onchromosome 7 colocalized with one allele of Wsb1/Nf1 on chromosome11. Omission of CCCTC-binding factor (CTCF) or deletion of thematernal ICR abrogated this association and altered Wsb1/Nf1gene expression. These findings demonstrate that CTCF mediatesan interchromosomal association, perhaps by directing distantDNA segments to a common transcription factory, and the dataprovide a model for long-range allele-specific associationsbetween gene regions on different chromosomes that suggest aframework for DNA recombination and RNA trans-splicing.
1 Medical Service, Department of Veterans Affairs, Palo Alto Health Care System, and Department of Medicine, Stanford University, Palo Alto, CA 94304, USA. 2 Departments of Pathology and Pediatrics, Stanford University, Stanford, CA 94305, USA.
* To whom correspondence should be addressed. E-mail: arhoffman{at}stanford.edu
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