Reduced representation bisulfite sequencing (RRBS) relies on the enrichment of CpG island-rich regions by MspI cleavage followed by size selection of 200-500/600 bps fragments. Consequently, only regions proximal to CpG islands are sequenced, while those with distant CpG islands are excluded from the analysis. This process, combined with bisulfite sequencing, allows for high-resolution detection of DNA methylation, and the sequencing approach, PE150, focuses specifically on the ends of the inserts rather than the middle, increasing the efficiency of methylation profiling.
This technique has emerged as a cost-effective and efficient alternative to Whole Genome Bisulfite Sequencing (WGBS) in DNA methylation research. While WGBS provides comprehensive insights by examining the entire genome at single base resolution, its high cost can be a limiting factor, which RRBS strategically mitigates this challenge by selectively analyzing a representative portion of the genome. This methodology is an invaluable tool that enables cost-effective DNA methylation research and advances knowledge of epigenetic mechanisms.