Chromatin dynamics in the regulation of CFTR expression

Nehal Gosalia, Ann Harris*

*Corresponding author for this work

Research output: Contribution to journalReview article

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)543-558
Number of pages16
JournalGenes
Volume6
Issue number3
DOIs
StatePublished - Jul 13 2015

Keywords

  • CFTR
  • Cis-regulatory elements
  • Higher order chromatin organization

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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