The active form of Mef2c promotes maturation of induced cardiomyocytes with p300 in direct cardiac reprogramming

Direct cardiac reprogramming converts fibroblasts into induced cardiomyocytes (iCMs) with the minimal combination of transcription factors, Gata4 (G), Mef2c (M), and Tbx5 (T). However, the induction of functional mature iCMs is inefficient and the mechanisms remain elusive. Mef2c is a central transcription factor in direct cardiac reprogramming. We investigated the effect of Mef2c isoforms(M1, M2, M6) and transcriptional activity (M2TAD) on cardiac reprogramming on cardiac reprogramming. Then, we found that the active form of Mef2c evoked epigenetic remodeling cooperating with p300 and promoted the maturation of iCMs. We analyzed global gene expression levels in GT/M1-, GT/M2-, GT/M6-, and GT/M2TAD-transduced MEFs at 1 week by microarray (Clariom S Array, Mouse, Affymetrix) according to the manufacturer’s instructions. Prior to analyses, all data were normalized by using a Single Space Transformation and Robust Multichip Analysis (SST-RMA) algorithm with Affymetrix Expression Console software version1.4.