Genomic Reorganization of Lamin-Associated Domains in Cardiac Myocytes is Associated with Differential Gene Expression and DNA Methylation in Human Dilated Cardiomyopathy [RNA-Seq]

Mutations in the LMNA gene causes set of disorders collectively referred to as laminopathies that include dilated cardiomyopathy. Lamin A/C proteins a components of nuclear lamina forms distinct nuclear domains called lamina associated domains (LADs). The roles of LADs in DCM is not known. To identify LADs and characterize their associations with CpG methylation and gene expression in human cardiac myocytes isolated from patients with DCM and controls we performed Chromatin immunoprecipitation-sequencing (ChIP-Seq), reduced representative bisulfite sequencing (RRBS), and RNA-sequencing (RNA-Seq) in 5 control and 5 DCM hearts with defined pathogenic variants in the LMNA gene. LADs are redistributed in DCM, are associated with CpG methylation and suppressed transcription, contributing to the pathogenesis of DCM in laminopathies. Overall design: integrated analysis of ChIP-seq for LMNA from Cardiac myocytes and RNA-seq and RRBS from 5 control and 5 DCM human heart sample

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Cheedipudi SM, Matkovich SJ, Coarfa C, Hu X, Robertson MJ, Sweet M, Taylor M, Mestroni L, Cleveland J, Willerson JT, Gurha P, Marian AJ