Reduced representation bisulfite sequencing (RRBS) of breast cancer cell lines

Breast cancers can be divided into subtypes with different prognoses and treatment responses based on global gene expression differences. This study utilized integrated analysis of DNA methylation, chromatin accessibility, transcription factor binding, and gene expression in large collections of breast cancer cell lines and patient tumors to identify transcription factors responsible for the basal-like gene expression program. The results of this study indicate that glucocorticoid receptor (GR) and signal transducer and activator of transcription 3 (STAT3) bind to the same genomic regulatory regions that are specifically open and unmethylated in basal-like breast cancer. These transcription factors cooperate to regulate expression of hundreds of genes in the basal-like gene expression signature and these downstream genes are associated with poor prognosis in patients. Overall design: To identify regulatory regions specific to basal-like breast cancer, reduced representation bisulfite sequencing (RRBS) was performed on 28 breast cancer cell lines (18 basal-like and 10 luminal) in order to measure DNA methylation across the genome.