Structural variation cooperates with permissive chromatin to control enhancer hijacking-mediated oncogenic transcription.

ABSTRACT: Structural variants (SVs) involving enhancer hijacking can rewire chromatin topologies to cause oncogene activation in human cancers, including hematologic malignancies; however, because of the lack of tools to assess their effects on gene regulation and chromatin organization, the molecular determinants for the functional output of enhancer hijacking remain poorly understood. Here, we developed a multimodal approach to integrate genome sequencing, chromosome conformation, chromatin state, and transcriptomic alteration for quantitative analysis of transcriptional effects and structural reorganization imposed by SVs in leukemic genomes. We identified known and new pathogenic SVs, including recurrent t(5;14) translocations that cause the hijacking of BCL11B enhancers for the allele-specific

SUBMITTER: Botten GA 

PROVIDER: S-EPMC10447518 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature