Methylated DNA immunoprecipitation sequencing (MeDIP-seq): Principles and applications

Methyl-DNA immunoprecipitation is used in combination with next generation sequencing (MeDIP-seq) as a genome-wide approach to enrich for and analyze methylated DNA. Fragmented DNA containing methylated cytosines is purified from genomic samples via an antibody to 5-methylcytosine (5mC), then sequenced and analyzed in order to detect peaks of differential methylation across the genomic landscape. Introduced more than a decade ago, MeDIP enrichment is considered a useful, repeatable, and affordable approach for methylation research. As next generation sequencing has become increasingly accessible and affordable, deep sequencing of the enriched DNA has replaced the initial use of microarrays. At this time, researchers consider MeDIP-seq a viable protocol to answer most questions about DNA methylation, providing single-base resolution is not required. Many well-established downstream analysis tools are also available, making MeDIP-seq a consistently popular option. As we continue to engage with highly complex methylomes, which may vary tremendously by cell-type, timepoint, and environment, we must focus on proper study design, larger cohorts, and judicious deployment of experimental controls in order to pull meaningful signals from background noise.