Andrew Smith
Assistant Professor
Department of Biological Sciences
University of Southern California
Examining the variation of intergenic hypomethylation in lung cancers
Focused promoter hyper-methylation and intergenic hypomethylation the two hallmarks of cancer methylomes. Promoter hyper-methylation is well known to alter expression of tumor suppressors, contributing to cancer phenotypes; intergenic hypomethylation has remained difficult to associate with function. Results from whole-genome shotgun bisulfite sequencing have suggested intergenic hypomethylation is organized as partially methylated domains (PMDs), with locations strongly conserved between methylomes. To investigate intergenic methylation loss in cancers more closely, we profiled DNA methylation using BS-seq in four lung cancer cell lines, along with two normal lung epithelial controls. Our results reveal a spectrum of both degree and genomic extent of intergenic hypomethylation. In the extreme, we observe virtually complete methylation loss through these so called “partially” methylated domains, with CpG-dense regions showing subtle resistance to this methylation loss. These observations will be discussed in the context of cell-to-cell heterogeneity and impact on transcription through the affected regions.
