UMMS Affiliation

Program in Gene Function and Expression; Department of Biochemistry and Molecular Pharmacology

Date

7-2010

Document Type

Article

Medical Subject Headings

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.

Comments

Citation: Nucleic Acids Res. 2010 Jul;38(13):4325-36. Epub 2010 Mar 31. Link to article on publisher's site

© 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.

Related Resources

Link to Article in PubMed