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Science 312 (5771): 269-272

Copyright © 2006 by the American Association for the Advancement of Science

CTCF Mediates Interchromosomal Colocalization Between Igf2/H19 and Wsb1/Nf1

Jian Qun Ling,1 Tao Li,1 Ji Fan Hu,1 Thanh H. Vu,1 Hui Ling Chen,1 Xin Wen Qiu,1 Athena M. Cherry,2 Andrew R. Hoffman1*

Abstract: Gene transcription may be regulated by remote enhancer or insulator regions through chromosome looping. Using a modification of chromosome conformation capture (3C) and fluorescence in situ hybridization, we found that one allele of the insulin-like growth factor 2 (Igf2)/H19 imprinting control region (ICR) on chromosome 7 colocalized with one allele of Wsb1/Nf1 on chromosome 11. Omission of CCCTC-binding factor (CTCF) or deletion of the maternal ICR abrogated this association and altered Wsb1/Nf1 gene expression. These findings demonstrate that CTCF mediates an interchromosomal association, perhaps by directing distant DNA segments to a common transcription factory, and the data provide a model for long-range allele-specific associations between gene regions on different chromosomes that suggest a framework 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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