UMMS Affiliation
Program in Gene Function and Expression; Department of Biochemistry and Molecular Pharmacology
Publication Date
2010-7
Document Type
Article
Subjects
Cell Line; Chromatin; Cystic Fibrosis Transmembrane Conductance Regulator; *Enhancer Elements, Genetic; Humans; Promoter Regions, Genetic; *Regulatory Sequences, Nucleic Acid
Disciplines
Genetics and Genomics
Abstract
Identification of regulatory elements and their target genes is complicated by the fact that regulatory elements can act over large genomic distances. Identification of long-range acting elements is particularly important in the case of disease genes as mutations in these elements can result in human disease. It is becoming increasingly clear that long-range control of gene expression is facilitated by chromatin looping interactions. These interactions can be detected by chromosome conformation capture (3C). Here, we employed 3C as a discovery tool for identification of long-range regulatory elements that control the cystic fibrosis transmembrane conductance regulator gene, CFTR. We identified four elements in a 460-kb region around the locus that loop specifically to the CFTR promoter exclusively in CFTR expressing cells. The elements are located 20 and 80 kb upstream; and 109 and 203 kb downstream of the CFTR promoter. These elements contain DNase I hypersensitive sites and histone modification patterns characteristic of enhancers. The elements also interact with each other and the latter two activate the CFTR promoter synergistically in reporter assays. Our results reveal novel long-range acting elements that control expression of CFTR and suggest that 3C-based approaches can be used for discovery of novel regulatory elements.
Rights and Permissions
© The Author(s) 2010. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI of Published Version
10.1093/nar/gkq175
Source
Nucleic Acids Res. 2010 Jul;38(13):4325-36. Epub 2010 Mar 31. Link to article on publisher's site
Journal/Book/Conference Title
Nucleic acids research
Related Resources
PubMed ID
20360044
Repository Citation
Gheldof, Nele; Smith, Emily M.; Tabuchi, Tomoko M.; Koch, Christoph M.; Dunham, Ian; Stamatoyannopoulos, John A.; and Dekker, Job, "Cell-type-specific long-range looping interactions identify distant regulatory elements of the CFTR gene" (2010). Program in Gene Function and Expression Publications and Presentations. 59.
https://escholarship.umassmed.edu/pgfe_pp/59
Comments
Co-author Emily Smith is a doctoral student in the Interdisciplinary Graduate Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.