Core mechanisms for epigenetic alteration of genomic DNA are hypermethylation of CpG islands in specific genes and global DNA hypomethylation. Region-specific DNA methylation plays an important role in the repression of gene transcription and is mainly found in 5’-CpG-3’dinucleotides within promoters or in the first exon of genes. Global DNA hypomethylation is likely caused by methyl-deficiency due to a variety of environmental influences. It has been demonstrated that alterations in DNA methylation are associated with many diseases, especially cancer. Highly specific isolation of methylated DNA combined with next generation sequencing for genome-wide methylation analysis should provide an advantage for convenient and comprehensive identification of methylation status of normal and diseased cells, such as cancer cells. Such analysis requires the isolated methylated DNA to contain minimal background in order to achieve high specificity (>98%) for reliably identifying true methylated regions. The major method for enriching methylated DNA used for genome-wide methylation profiling is methylated DNA immunoprecipitation (MeDIP). However, currently used MeDIP methods, represented by most commercially available kits, have significant weaknesses including highly non-specific enrichment (amount of enriched DNA is >75% of the amount of input DNA), time consuming, labor intensive, and has low throughput. Thus, for effectively and specifically capturing methylated DNA used for next generation sequencing analysis, an ideal MeDIP method requires maximum sensitivity with minimal background levels. TheMeDIP Ultra Kit is designed to achieve these goals by maximizing sensitivity and minimizing non-specific background signals, and is a significant improvement over previous MeDIP kits.