UC San Diego

BCL6 is an oncogene that is known as the principle driver of non-Hodgkin’s Lymphoma. This gene also plays a role in skeletal muscle development, metabolism, and function. Several histologic stains, such as the Crystal Violet Assay, and Jenner-Giemsa stain identifies BCL6 pharmacology as a potent modulator of in vitro muscle development. There is additional evidence, based on apoptotic, cell cycle markers, and expression of differentiation genes that support this idea. To test this, a competitive inhibitor, FX1, was used to block the SMRT/NCOR corepressor complex from binding the BTB domain of the BCL6 gene. This drug was applied to C2C12 myoblasts to block this corepressor complex, which recruits HDACs to repress genes downstream the BCL6 gene. In the various stains and qPCR analysis, the drug-treated groups displayed a decreased number of cells due to either apoptosis or a lack of cell cycle gene expression. The data and existing literature suggest that BCL6 may play a role in apoptotic pathways related to skeletal muscle development. Additionally, there are studies that link BCL6 to fatty acid metabolism and this was investigated using the Agilent Seahorse XF Mito Stress Test to measure the OCR:ECAR ratios of C2C12 myoblasts and wildtype primary myoblasts. The assay suggests that the inhibition of BCL6 results in cells utilizing glycolysis as their main fuel source, instead of fatty acid metabolism under mitochondrial stress. Further understanding of the role of BCL6 in skeletal muscle development and metabolism provides possible therapies and treatments for muscular dystrophies and metabolic diseases.