TY - JOUR TI - Genome-wide quantification of the effects of DNA methylation on human gene regulation AU - Lea, Amanda J AU - Vockley, Christopher M AU - Johnston, Rachel A AU - Del Carpio, Christina A AU - Barreiro, Luis B AU - Reddy, Timothy E AU - Tung, Jenny A2 - Ponting, Chris P A2 - Weigel, Detlef A2 - Aerts, Stein VL - 7 PY - 2018 DA - 2018/12/21 SP - e37513 C1 - eLife 2018;7:e37513 DO - 10.7554/eLife.37513 UR - https://doi.org/10.7554/eLife.37513 AB - 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. KW - DNA methylation KW - epigenomics KW - high-throughput reporter assay JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -