Is c-myc super-enhancer invasion associated with aberrant chromatin interactions in cancer?

• Main Author: Fu, Shufeng
• Other Authors: Melissa Fullwood
• Format: Final Year Project
• Language: English
• Published: 2017
• Subjects: DRNTU::Science
• Online Access: http://hdl.handle.net/10356/70881
• Institution: Nanyang Technological University

c-Myc is an oncogenic transcription factor being over-expressed in approximately 70% of human cancers. However, c-Myc is notoriously an “undruggable’ target and its inhibition is complex. In general, super-enhancer is a collection of enhancers with a stronger enrichment of transcription factor binding sites as compared to enhancers. Chromatin interactions bring promoters and enhancers/super-enhancers into close proximity to activate or raise transcription, thus playing an essential role in gene regulation. Taking into account of abnormal gene expression being a key characteristic of cancers and hinging on the phenomenon of high c-Myc super-enhancer invasion, the study aims to identify aberrant cancer-specific chromatin interactions which upregulate target genes under high c-Myc conditions, by using Circular Chromosome Conformation Capture (4C). Our results have shown chromatin interactions between c-Myc bound super-enhancers and RUNX3, NSMCE1, IL4R and IL21R promoters. The significance of an upregulation of these genes in cancer are mostly in consensus with published studies. Hence, based on preliminary results, our study shows that c-Myc super-enhancer invasion is associated with aberrant chromatin interactions which upregulate target genes. However, further work is required to confirm the hypothesis.