for this is to align with two separate C→U or G→A substituted genome sequences, one to model methylation for each of the two strands. Results showed a global increase in methylation, particularly near transcription start sites (TSS) and CpG islands, in agreement with overall levels of methylation determined on unfractionated DNA. Ideally, increased methylation of promoters or nearby CpG islands should be associated with decreased mRNA expression levels.