Whole-genome DNA methylation profiling with nucleotide resolution

Abstract

In many eukaryotic organisms, methylation at the fifth carbon of cytosine (5mC) is a stable epigenetic mark crucial for many biological processes, including cell differentiation, X-chromosome inactivation, transposon silencing, and genomic imprinting. DNA methylation can be stably inherited to the subsequent generation. It can also change dynamically in response to developmental cues or environmental stimuli, and is an important regulator for developmental switch and cell fate determination. Consequently, many human diseases are associated with aberrant DNA methylation. Gene-specific methylation analysis by sequencing of bisulfite-treated genomic DNA has been instrumental in understanding how DNA methylation affects gene transcription. In recent years, techniques have been developed for genome-wide 5mC detection, and complete methylome at single base resolution has been reported for several organisms, providing unprecedented details on the dynamic nature of DNA methylation during development. With the advance in high-throughput sequencing and the availability of genome sequences, mapping the methylome for species with complex genomes has become increasingly feasible.