Poster abstracts

Poster number 59 submitted by Auinash Kalsotra

Loss of Mef2 expression reactivates the embryonic cardiac microRNA program in myotonic dystrophy type 1

Auinash Kalsotra (Biochemistry and Medical Biochemistry, Institute of Genomic Biology), Ravi K Singh (Pathology, Baylor College of Medicine), Priyatansh Gurha (Human and Molecular Genetics, Baylor College of Medicine), Amanda J Ward (Pathology, Baylor College of Medicine), Chad J. Creighton (The Dan L. Duncan Cancer Center, Baylor College of Medicine), Thomas A. Cooper (Pathology, Molecular & Cellular Biology, Baylor College of Medicine)

Abstract:
Cardiac dysfunction is the second leading cause of death in myotonic dystrophy type 1 (DM1). A screen of more than 500 miRNAs in a DM1 mouse model identified 54 miRNAs that were differentially expressed in heart. More than 80% exhibited down regulation towards the embryonic expression pattern and showed a DM1-specific response. Twenty of the 22 miRNAs tested were also significantly down regulated in DM1 human heart tissue. We found that a large proportion of these miRNA are Mef2 transcriptional targets. MEF2A and MEF2C protein expression is significantly reduced in both human DM1 heart samples and the mouse model. Exogenous Mef2C expression restores normal levels of Mef2 target miRNAs and mRNAs in a DM1 cardiac cell culture model. These results indicate that mis-regulation of cardiac Mef2 circuitry is causal to the reprogramming of gene expression in DM1.

Keywords: Alternative splicing, microRNA, Myotonic Dystrophy