Genome-wide quantification of the effects of DNA methylation on human gene regulation.

Journal Article (Journal Article)

Changes in DNA methylation are involved in development, disease, and the response to environmental conditions. However, not all regulatory elements are functionally methylation-dependent (MD). Here, we report a method, mSTARR-seq, that assesses the causal effects of DNA methylation on regulatory activity at hundreds of thousands of fragments (millions of CpG sites) simultaneously. Using mSTARR-seq, we identify thousands of MD regulatory elements in the human genome. MD activity is partially predictable using sequence and chromatin state information, and distinct transcription factors are associated with higher activity in unmethylated versus methylated DNA. Further, pioneer TFs linked to higher activity in the methylated state appear to drive demethylation of experimentally methylated sites. MD regulatory elements also predict methylation-gene expression relationships across individuals, where they are 1.6x enriched among sites with strong negative correlations. mSTARR-seq thus provides a map of MD regulatory activity in the human genome and facilitates interpretation of differential methylation studies.

Full Text

Duke Authors

Cited Authors

  • Lea, AJ; Vockley, CM; Johnston, RA; Del Carpio, CA; Barreiro, LB; Reddy, TE; Tung, J

Published Date

  • December 21, 2018

Published In

Volume / Issue

  • 7 /

PubMed ID

  • 30575519

Pubmed Central ID

  • PMC6303109

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.37513


  • eng

Conference Location

  • England