Abstract 18784: Lamin A/C Regulates Transcription Factor and Epigenetic Gene Networks in the Heart

Introduction: Mutations in Lamin A/C (LMNA) are major causes of dilated cardiomyopathy (DCM). LMNA an inner nuclear membrane protein is considered to be essential for nuclear genome organization and gene expression. However, the role of LMNA in regulation of gene expression in the heart and particularly in DCM is unknown. Objectives: To identify and define the gene regulatory networks governed by LMNA in the heart. Results: RNA sequencing was performed in 2-week old LMNA-deficient (Lmna-/-) and wild type (WT) littermates, prior to cardiac dysfunction. 2088 genes (929 up /1159 down at FDR 5%) were dysregulated in Lmna-/- as compared to WT hearts. Bioinformatics analysis identified Histone H3K4 demethylases KDM5A and KDM5B, transcription factor/coactivators Nuclear protein 1(NUPR1), Forkhead box protein (FOXO4), and Tripartite Motif Containing 24 (TRIM24) among the activated transcriptional regulators in the Lmna-/- mouse hearts. Whereas, Retinoblastoma1 (RB1) and E2F targets were suppressed. Pathway analys...