TY - JOUR
T1 - Identifying and mapping cell-type-specific chromatin programming of gene expression
AU - Marstrand, Troels T.
AU - Storey, John D.
PY - 2014/2/11
Y1 - 2014/2/11
N2 - 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 and genomewide gene-expression levels in 20 diverse human cell types. 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., ±200 kb) capture more genes with this relationship than local regions (e.g., ±2.5 kb), 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 uses. This quantitative framework is likely applicable to other settings aimed at relating continuous genomic measurements to gene-expression variation.
AB - 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 and genomewide gene-expression levels in 20 diverse human cell types. 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., ±200 kb) capture more genes with this relationship than local regions (e.g., ±2.5 kb), 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 uses. This quantitative framework is likely applicable to other settings aimed at relating continuous genomic measurements to gene-expression variation.
KW - Association
KW - Computational biology
KW - Encode
KW - Epigenetics
KW - Gene regulation
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U2 - 10.1073/pnas.1312523111
DO - 10.1073/pnas.1312523111
M3 - Article
C2 - 24469817
AN - SCOPUS:84893865070
SN - 0027-8424
VL - 111
SP - E645-E654
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 6
ER -