Comprehensive Predictions of Mef2-Mediated Chromatin Loops, Which May Inhibit Ubx Binding by Blocking Low-Affinity Binding Sites

Gene regulation depends on the interaction between chromatin-associated factors, such as transcription factors (TFs), which promote chromatin loops to ensure tight contact between enhancer and promoter regions. So far, positive interactions that lead to gene activation have been the main focus of research, but regulations related to blocking or inhibiting factor binding are also essential to maintaining a defined cellular status. To understand these interactions in greater detail, I investigated the possibility of the muscle differentiation factor Mef2 to prevent early Hox factor binding, leading to the proper timing of regulatory processes and the activation of differentiation events. My investigations relied on a collection of publicly available genome-wide binding data sets of Mef2 and Ubx (as the Hox factor), Capture-C interactions, and ATAC-seq analysis in Mef2 mutant cells. The analysis indicated that Mef2 can form possible chromatin loops to Ubx-bound regions. These regions contain low-affinity Ubx binding sites, and the chromatin architecture is independent of Mef2’s function. High levels of Ubx may disrupt the loops and allow specific Ubx bindings to regulate defined targets. In summary, my investigations highlight that the use of many publicly available data sets enables computational approaches to make robust predictions and, for the first time, suggest a molecular function of Mef2 as a preventer of Hox binding, indicating that it may act as a timer for muscle differentiation.