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| Status |
Public on Nov 08, 2013 |
| Title |
A genome-wide analysis of open chromatin in human tracheal epithelial cells reveals novel candidate regulatory elements for lung function (DNase-hypersensitivity) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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. 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. Genes with THE-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. 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.
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| Overall design |
To identify cis-regulatory elements for genes expressed in human tracheal epithelial cells we generated genome-wide maps of open chromatin by DNase-seq. HTE cells were isolated from these trachea and grown as described previously (Davis P.B. et al.1990).
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| Contributor(s) |
Bischof JM, Ott CJ, Leir SH, Gosalia N, Song L, London D, Furey TS, Cotton CU, Crawford GE, Harris A |
| Citation(s) |
22169360 |
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| Submission date |
Nov 07, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Ann Harris |
| Organization name |
Lurie Children's Hospital of Chicago Research Center
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| Street address |
2430 N Halsted Street Box 211
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| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60614 |
| Country |
USA |
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| Platforms (1) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE52181 |
A genome-wide analysis of open chromatin in human tracheal epithelial cells reveals novel candidate regulatory elements for lung function |
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| Relations |
| BioProject |
PRJNA227110 |
| SRA |
SRP032784 |
