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

TL;DR

This study presents a quantitative framework to map how chromatin structure variations influence gene expression across different human cell types, revealing that a significant portion of gene expression differences are explained by chromatin accessibility.

Contribution

The paper introduces a novel framework for linking high-resolution chromatin structure data to gene expression, emphasizing the importance of distal regions and cell-type specific hypersensitive sites.

Findings

Approximately 25% of genes have cell-type specific expression explained by chromatin structure.

Distal chromatin regions capture more genes with expression relationships than local regions.

Identified hypersensitive sites are contextually diverse and linked to cell-type specific expression.

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.