Epigenetic modifications on the DNA sequence (DNA methylation) or on 
chromatin-associated proteins (i.e., histones) comprise the "cellular 
epigenome"; together these modifications play an important role in the 
regulation of gene expression. Unlike the genome, the epigenome is highly 
variable between cells and is dynamic and plastic in response to cellular stress 
and environmental cues. The role of the epigenome, specifically, the methylome 
has been increasingly highlighted and has been implicated in many cellular and 
developmental processes such as embryonic reprogramming, cellular 
differentiation, imprinting, X chromosome inactivation, genomic stability, and 
complex diseases such as cancer. Over the past decade several methods have been 
developed and applied to characterize DNA methylation at gene-specific loci 
(using either traditional bisulfite sequencing or pyrosequencing) or its 
genome-wide distribution (microarray analysis following methylated DNA 
immunoprecipitation (MeDIP-chip), analysis by sequencing (MeDIP-seq), reduced 
representation bisulfite sequencing (RRBS), or shotgun bisulfite sequencing). 
This chapter reviews traditional bisulfite sequencing and shotgun bisulfite 
sequencing approaches, with a greater emphasis on shotgun bisulfite sequencing 
methods and data analysis.