Genome-wide quantification of the effects of DNA methylation on human gene regulation
Genome-wide quantification of the effects of DNA methylation on human gene regulation
Abstract Changes in DNA methylation are important in development and disease, but not all regulatory elements act in a methylation-dependent (MD) manner. Here, we developed mSTARR-seq, a high-throughput approach to quantify the effects of DNA methylation on regulatory element function. We assay MD activity in 14% of the euchromatic human genome, identify 2,143 MD regulatory elements, and predict MD activity using sequence and chromatin state information. We identify transcription factors associated with higher activity in unmethylated or methylated states, including an association between pioneer transcription factors and methylated DNA. Finally, we use mSTARR-seq to predict DNA methylation-gene expression correlations in primary cells. Our findings provide a map of MD regulatory activity across the human genome, facilitating interpretation of the many emerging associations between methylation and trait variation.
Lea Amanda J.、Barreiro Luis B.、Reddy Timothy E.、Vockley Christopher M.、Del Carpio Christina A.、Johnston Rachel A.、Tung Jenny
Lewis-Sigler Institute for Integrative Genomics, Carl Icahn LaboratoryDepartment of Pediatrics, Sainte-Justine Hospital Research Centre, University of MontrealCenter for Genomic and Computational Biology, Duke University Medical School||Department of Biostatistics and Bioinformatics, Duke University Medical School||Program in Computational Biology and Bioinformatics, Duke UniversityCenter for Genomic and Computational Biology, Duke University Medical School||Department of Biostatistics and Bioinformatics, Duke University Medical SchoolDepartment of Evolutionary Anthropology, Duke UniversityDepartment of Evolutionary Anthropology, Duke UniversityLewis-Sigler Institute for Integrative Genomics, Carl Icahn Laboratory||Department of Evolutionary Anthropology, Duke University||Institute of Primate Research, National Museums of Kenya||Duke University Population Research Institute, Duke University||Department of Biology, Duke University
遗传学分子生物学生物科学研究方法、生物科学研究技术
Lea Amanda J.,Barreiro Luis B.,Reddy Timothy E.,Vockley Christopher M.,Del Carpio Christina A.,Johnston Rachel A.,Tung Jenny.Genome-wide quantification of the effects of DNA methylation on human gene regulation[EB/OL].(2025-03-28)[2025-05-23].https://www.biorxiv.org/content/10.1101/146829.点此复制
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