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

Troels T. Marstrand, John D. Storey

Research output: Contribution to journalArticle

10 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)E645-E654
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number6
DOIs
StatePublished - Feb 11 2014

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Association
  • Computational biology
  • Encode
  • Epigenetics
  • Gene regulation

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