Super-enhancers (SEs) are large (2 to >100 kilobases) DNA elements that control cell identity and disease. These unusual elements are occupied by high levels of key transcription factors, co-activators and chromatin regulators. SEs are hot spots for sequence variations associated with many human diseases, including cancer. Surprisingly, SEs are transcribed at high levels into RNAs (seRNAs). However, little is known about the biogenesis, structural identity and function of these seRNAs. Preliminary evidence suggests that seRNAs are components of SE complexes, composed of chromatin, RNAs and transcription factors, which play critical roles in controlling expression of key master cell-type-specific transcription factors and disease-causing genes. Our main objectives are to characterize the biogenesis of seRNAs, to determine the composition of RNA-protein complexes associated with seRNAs and to investigate the functions of seRNAs in gene regulation. We are focusing on the c-MYC and RUNX1 SEs, drivers of two cancers originating from B and T cells of the immune system: multiple myeloma (MM) and T-cell acute lymphoblastic leukemia (T-ALL), respectively. By uncovering the biogenesis and functions of seRNAs at the molecular level, our results may identify novel targets for new therapies for MM and T-ALL, as well as other cancers. New ways to modulate the immune response may also be revealed by our studies.
Citation Format: Yang Eric Guo, Richard Young. Biogenesis and regulatory functions of super-enhancer RNAs in cancer cells of the immune system. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A166.
- ©2016 American Association for Cancer Research.