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Identifying and mapping cell-type-specific chromatin programming of gene expression

Author(s): Marstrand, Troels T; Storey, John D

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Abstract: A problem of substantial interest is to systematically map variation in chromatin structure to gene expression regulation across conditions, environments, or differentiated cell types. We developed and applied a quantitative framework for determining the existence, strength, and type of relationship between high-resolution chromatin structure in terms of DNaseI hypersensitivity (DHS) and genome-wide gene expression levels in 20 diverse human cell lines. We show that ∼25% of genes show cell-type specific expression explained by alterations in chromatin structure. We find that distal regions of chromatin structure (e.g., ±200kb) capture more genes with this relationship than local regions (e.g., ±2.5kb), yet the local regions show a more pronounced effect. By exploiting variation across cell-types, we were capable of pinpointing the most likely hypersensitive sites related to cell-type specific expression, which we show have a range of contextual usages. This quantitative framework is likely applicable to other settings aimed at relating continuous genomic measurements to gene expression variation.
Publication Date: 11-Feb-2014
Electronic Publication Date: 27-Jan-2014
Citation: Marstrand, Troels T, Storey, John D. (2014). Identifying and mapping cell-type-specific chromatin programming of gene expression. Proceedings of the National Academy of Sciences, 111 (6), E645 - E654. doi:10.1073/pnas.1312523111
DOI: doi:10.1073/pnas.1312523111
ISSN: 0027-8424
EISSN: 1091-6490
Pages: E645 - E654
Type of Material: Journal Article
Journal/Proceeding Title: Proceedings of the National Academy of Sciences
Version: Author's manuscript

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