Understanding Long Range Chromosomal Contacts and Perturbing Them to Treat Childhood Diseases
Researchers are pursing questions of how chromatin is organized in the nucleus, specifically, how enhancer-promoter contacts are formed. They have found that the hematopoietic transcription factor GATA1 and its co-factor FOG1 are essential to juxtapose the enhancer of the beta globin locus with the promoter.
This study was among the first to define any nuclear factor in chromatin looping. We discovered that chromatin looping is highly dynamic and can occur even at repressed genes. Using a novel approach of tethering candidate looping factors to an endogenous gene, researchers were for the first time able to generate an enhancer-promoter chromatin loop at a native endogenous gene locus and thus discovered that chromatin looping causally underlies gene expression.
Subsequently, the approach was adapted to reprogram the murine and human beta globin loci to reactivate the dormant embryonic and fetal globin genes, respectively. Researchers are in the process of advancing this strategy towards a clinical application in the setting of sickle cell anemia and beta thalassemia.