B cell super-enhancers and regulatory clusters recruit AID tumorigenic activity

ABSTRACT: The antibody gene mutator AID promiscuously damages oncogenes and B cell identity genes leading to chromosomal translocations and tumorigenesis. Why non-immunoglobulin loci are susceptible to AID activity is unknown. Here we study AID-mediated lesions in the context of nuclear architecture and the B cell regulome. We show that AID targets are not randomly distributed across the genome, but are predominantly clustered within super-enhancers. Unexpectedly, in these domains AID deaminates highly active promoters and eRNA+ enhancers interconnected in some instances over megabases of linear chromatin. Using genome editing we demonstrate that 3D-linked targets cooperate to recruit AID-mediated breaks. Furthermore, a comparison of hypermutation in mouse B cells, AID-induced kataegis in human lymp

ORGANISM(S): Mus musculus

SUBMITTER: Marei Dose 

PROVIDER: E-GEOD-62063 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress