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A problem of substantial interest is to systematically map variation inchromatin structure to gene expression regulation across conditions,environments, or differentiated cell types. We developed and applied aquantitative framework for determining the existence, strength, and type ofrelationship between high-resolution chromatin structure in terms of DNaseIhypersensitivity (DHS) and genome-wide gene expression levels in 20 diversehuman cell lines. We show that ~25% of genes show cell-type specific expressionexplained by alterations in chromatin structure. We find that distal regions ofchromatin structure (e.g., +/- 200kb) capture more genes with this relationshipthan local regions (e.g., +/- 2.5kb), yet the local regions show a morepronounced effect. By exploiting variation across cell-types, we were capableof pinpointing the most likely hypersensitive sites related to cell-typespecific expression, which we show have a range of contextual usages. Thisquantitative framework is likely applicable to other settings aimed at relatingcontinuous genomic measurements to gene expression variation.

Identifying and Mapping Cell-type Specific Chromatin Programming of Gene Expression