  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.

Quantitative Methods;Genomics;Applications;Methodology