Seth Cheetham, Mater Research Institute, Australia
In cancers, but not healthy tissues, LINE-1 “jumping genes” insert throughout the genome, sometimes activating oncogenes and disrupting tumour suppressor genes. While CpG methylation regulates LINE-1 activity, the locus-specific methylation landscape of mobile human TEs has to date proven largely inaccessible. Here, we apply long-read nanopore sequencing and computational tools to directly infer CpG methylation of LINE-1s in healthy and cancerous tissues. We find pronounced demethylation of LINE-1s in cancer, allele-specific LINE-1 methylation, tumour-specific insertions, and demethylation of aberrantly expressed young LINE-1s in normal tissues. Finally, using nanopore-based chromatin accessibility profiling, we investigate the factors controlling LINE-1 activation in cancer.
Dr. Seth Cheetham is an NHMRC Early Career Fellow in Professor Geoffrey Faulkner’s Group at Mater Research Institute-University of Queensland. For his PhD he worked with Professor Andrea Brand at the University of Cambridge developing novel methods to elucidate mechanisms of gene regulation. Dr. Cheetham’s current research focuses on deciphering the functions of repetitive elements in cancer using novel tools including third-generation sequencing platforms and DamID-based approaches.