Enhancer RNA functions
Enhancers are DNA elements that govern spatial and temporal regulation of gene expression during development and disease. We and others have identified noncoding RNAs that are transcribed from tissue and disease-specific enhancers termed enhancer RNAs (eRNAs). Enhancer RNA transcription is considered to be indispensable for target gene transcription. However, the exact mechanism(s) by which eRNAs activate their target promoters is unclear. We have shown that Integrator facilitates transcription of eRNAs and mediates their 3′-end processing. Therefore, it will be important to dissect the interplay between Integrator, enhancer structure/function and eRNAs during normal development and following disease.
Aberrant regulation of enhancers is considered to be a key event in the genesis and progression of cancer. We are using a verity of genome-wide approaches to develop an atlas of disease-induced enhancers in multiple cancers with activating mutations in KRAS and BRAF. Next, we will target these disease-induced eRNAs with anti-sense oligonucleotides (ASOs) to silence cancer-causing genes as a transformative treatment in cancer. We hope such ‘Enhancer RNA Therapy’ will be able to overcome resistance to chemotherapy, targeted-therapy and further enhance precision medicine.