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Genes 2015, 6(3), 543-558; doi:10.3390/genes6030543

Chromatin Dynamics in the Regulation of CFTR Expression

1,2
and
1,2,*
1
Human Molecular Genetics Program, Lurie Children's Research Center, Chicago, IL 60614, USA
2
Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Jessica Tyler
Received: 15 May 2015 / Revised: 3 July 2015 / Accepted: 7 July 2015 / Published: 13 July 2015
(This article belongs to the Special Issue Chromatin Dynamics)
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Abstract

The contribution of chromatin dynamics to the regulation of human disease-associated loci such as the cystic fibrosis transmembrane conductance regulator (CFTR) gene has been the focus of intensive experimentation for many years. Recent technological advances in the analysis of transcriptional mechanisms across the entire human genome have greatly facilitated these studies. In this review we describe the complex machinery of tissue-specific regulation of CFTR expression, and put earlier observations in context by incorporating them into datasets generated by the most recent genomics methods. Though the gene promoter is required for CFTR expression, cell-type specific regulatory elements are located elsewhere in the gene and in flanking intergenic regions. Probably within its own topological domain established by the architectural proteins CTCF and cohesin, the CFTR locus utilizes chromatin dynamics to remodel nucleosomes, recruit cell-selective transcription factors, and activate intronic enhancers. These cis-acting elements are then brought to the gene promoter by chromatin looping mechanisms, which establish long-range interactions across the locus. Despite its complexity, the CFTR locus provides a paradigm for elucidating the critical role of chromatin dynamics in the transcription of individual human genes. View Full-Text
Keywords: CFTR; cis-regulatory elements; higher order chromatin organization CFTR; cis-regulatory elements; higher order chromatin organization
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Gosalia, N.; Harris, A. Chromatin Dynamics in the Regulation of CFTR Expression. Genes 2015, 6, 543-558.

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