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A genome-wide analysis of open chromatin in human tracheal epithelial cells reveals novel candidate regulatory elements for lung function.

Publication ,  Journal Article
Bischof, JM; Ott, CJ; Leir, S-H; Gosalia, N; Song, L; London, D; Furey, TS; Cotton, CU; Crawford, GE; Harris, A
Published in: Thorax
May 2012

BACKGROUND: Distal cell-type-specific regulatory elements may be located at very large distances from the genes that they control and are often hidden within intergenic regions or in introns of other genes. The development of methods that enable mapping of regions of open chromatin genome wide has greatly advanced the identification and characterisation of these elements. METHODS: Here we use DNase I hypersensitivity mapping followed by deep sequencing (DNase-seq) to generate a map of open chromatin in primary human tracheal epithelial (HTE) cells and use bioinformatic approaches to characterise the distribution of these sites within the genome and with respect to gene promoters, intronic and intergenic regions. RESULTS: Genes with HTE-selective open chromatin at their promoters were associated with multiple pathways of epithelial function and differentiation. The data predict novel cell-type-specific regulatory elements for genes involved in HTE cell function, such as structural proteins and ion channels, and the transcription factors that may interact with them to control gene expression. Moreover, the map of open chromatin can identify the location of potentially critical regulatory elements in genome-wide association studies (GWAS) in which the strongest association is with single nucleotide polymorphisms in non-coding regions of the genome. We demonstrate its relevance to a recent GWAS that identifies modifiers of cystic fibrosis lung disease severity. CONCLUSION: Since HTE cells have many functional similarities with bronchial epithelial cells and other differentiated cells in the respiratory epithelium, these data are of direct relevance to elucidating the molecular basis of normal lung function and lung disease.

Duke Scholars

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Published In

Thorax

DOI

EISSN

1468-3296

Publication Date

May 2012

Volume

67

Issue

5

Start / End Page

385 / 391

Location

England

Related Subject Headings

  • Trachea
  • Respiratory System
  • Respiratory Mucosa
  • Lung
  • Humans
  • High-Throughput Nucleotide Sequencing
  • Genome-Wide Association Study
  • Gene Expression Regulation
  • Epithelial Cells
  • Deoxyribonuclease I
 

Citation

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ICMJE
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Bischof, J. M., Ott, C. J., Leir, S.-H., Gosalia, N., Song, L., London, D., … Harris, A. (2012). A genome-wide analysis of open chromatin in human tracheal epithelial cells reveals novel candidate regulatory elements for lung function. Thorax, 67(5), 385–391. https://doi.org/10.1136/thoraxjnl-2011-200880
Bischof, Jared M., Christopher J. Ott, Shih-Hsing Leir, Nehal Gosalia, Lingyun Song, Darin London, Terrence S. Furey, Calvin U. Cotton, Gregory E. Crawford, and Ann Harris. “A genome-wide analysis of open chromatin in human tracheal epithelial cells reveals novel candidate regulatory elements for lung function.Thorax 67, no. 5 (May 2012): 385–91. https://doi.org/10.1136/thoraxjnl-2011-200880.
Bischof JM, Ott CJ, Leir S-H, Gosalia N, Song L, London D, et al. A genome-wide analysis of open chromatin in human tracheal epithelial cells reveals novel candidate regulatory elements for lung function. Thorax. 2012 May;67(5):385–91.
Bischof, Jared M., et al. “A genome-wide analysis of open chromatin in human tracheal epithelial cells reveals novel candidate regulatory elements for lung function.Thorax, vol. 67, no. 5, May 2012, pp. 385–91. Pubmed, doi:10.1136/thoraxjnl-2011-200880.
Bischof JM, Ott CJ, Leir S-H, Gosalia N, Song L, London D, Furey TS, Cotton CU, Crawford GE, Harris A. A genome-wide analysis of open chromatin in human tracheal epithelial cells reveals novel candidate regulatory elements for lung function. Thorax. 2012 May;67(5):385–391.

Published In

Thorax

DOI

EISSN

1468-3296

Publication Date

May 2012

Volume

67

Issue

5

Start / End Page

385 / 391

Location

England

Related Subject Headings

  • Trachea
  • Respiratory System
  • Respiratory Mucosa
  • Lung
  • Humans
  • High-Throughput Nucleotide Sequencing
  • Genome-Wide Association Study
  • Gene Expression Regulation
  • Epithelial Cells
  • Deoxyribonuclease I