Acute intervention reveals critical roles of BAF, KMT2D and p300 in MyoD binding on enhancers

Previous studies using constitutive expression of transcription factors (TFs) and genetic knockout of cofactors have revealed important roles of chromatin remodeler BAF, H3K4me1 methyltransferase KMT2D, and H3K27 acetyltransferase p300 in enhancer regulation. However, binding dynamics of these cofactors and TFs on enhancers remain unclear. Here we show that within one hour of its nuclear translocation, the master myogenic TF MyoD is co-localized with BAF, KMT2D, and p300 on over half of MyoD+ enhancers. Acute depletion of KMT2D protein disrupts de novo binding of MyoD, BAF, and p300 on enhancers. Short-term inhibition of BAF or p300 enzymatic activity dramatically reduces de novo binding of MyoD, BAF, KMT2D, and p300 on enhancers. Together, these results highlight the interdependency of MyoD and chromatin regulators BAF, KMT2D and p300 in their binding to enhancers. Our data also suggest that p300 may hold a more prevailing role than previously reported.