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ATAC-seq of human lung cell types

ABSTRACT: We report the application of the assay for transposase-accessible chromatin using sequencing (ATAC-seq) for the profiling of open chromatin human primary lung cell types implicated in lung disease pathology, such as chronic obstructive pulmonary disease. We generated chromatin accessibility profiles for human primary bronchial epithelial cells, small airway epithelial cells, alveolar type II pneumocytes, and lung fibroblasts using Omni-ATAC-seq. We further profiled open chromatin in a commonly used bronchial epithelial cell line (16HBE14o-) to evaluate the correlation with primary cell profiles and confirm the technical improvements using Omni-ATAC-seq vs Fast-ATAC-seq. We used these profiles to evaluate the enrichment of COPD risk variants in lung-specific open chromatin regions (OCRs) and generated cell type-specific regulatory predictions for >6,500 variants corresponding to 82 COPD GWAS loci.

ORGANISM(S): Homo sapiens

PROVIDER: GSE152779 | GEO | 2021/04/02

REPOSITORIES: GEO

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Project description: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. HTE (human tracheal epithelial) cells were isolated from human trachea postmortem and grown as described previously (Davis P.B. et al.1990). Total RNA was extracted by Trizol and the samples shipped to NimbleGen for gene expression analysis on NimbleGen 4 X 72K HG18 60mer arrays.

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ATAC-seq of human lung cell types

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