The Mef2 Transcription Network Is Disrupted in Myotonic Dystrophy Heart Tissue, Dramatically Altering miRNA and mRNA Expression

• DOI: 10.1016/j.celrep.2013.12.025
• Publication Date: 2014-01-09T15:45:23Z
• Authors: Auinash Kalsotra; Ravi K. Singh; Priyatansh Gurha; Amanda J. Ward; Chad J. Creighton; Thomas A. Cooper
• Keywords: MEF2C; Mef2

Cardiac dysfunction is the second leading cause of death in myotonic dystrophy type 1 (DM1), primarily because arrhythmias and cardiac conduction defects. A screen more than 500 microRNAs (miRNAs) a DM1 mouse model identified 54 miRNAs that were differentially expressed heart. More 80% exhibited downregulation toward embryonic expression pattern showed DM1-specific response. total 20 22 tested also significantly downregulated human heart tissue. We demonstrate many these are direct MEF2 transcriptional targets, including for which depletion associated with or fibrosis. protein reduced both samples, exogenous MEF2C restores normal levels target mRNAs cell culture model. conclude loss causes pathogenic features through aberrant miRNA mRNA targets.