Epigenetic Regulation by APOBEC3B in Cancer

Cancer cells differ from their normal counterparts by genetic mutations, as well as by epigenetic changes in DNA methylation and chromatin accessibility profiles. The APOBEC3B cytosine deaminase is overexpressed in a large variety of tumors, including breast, lung, ovarian, hematologic and head/neck cancers. APOBEC3B has been shown to mutate the cancer genome via its deamination activity, however it is unknown whether it additionally affects the epigenetic profile of these cells. Our biochemical studies show that APOBEC3B can deaminate methylated cytosines, making it a good candidate to act as a modifier of DNA methylation in cancer cells where APOBEC3B is overexpressed. Using CRISPR-Cas9, we created isogenic APOBEC3B-expressing and null cancer cells. These cells are being utilized for reduced representation bisulfite sequencing (RRBS) screens to identify regions in the genome which have APOBEC3B dependent methylation patterns, as well as RNA-seq to study downstream expression changes. We will discuss the analyses and findings of our ongoing studies.