Alteration of epigenetic landscape by lamin A mutations: Hallmark of Dilated Cardiomyopathy

Abstract

Mutations in lamin A have been reported to be associated with over 16 human diseases including dilated cardiomyopathy (DCM). We have focused on three such DCM causing mutants of lamin A which have to address the contribution of lamins in the pathogenesis of DCM at molecular level. We have elucidated the effect of these mutants for the first time on the epigenetic landscape of a myogenic fibroblast cell line C2C12. C2C12 cells expressing these mutant proteins exhibited alterations in some histone modification marks like H3K4me3, H3K9me3, H3K27me3, H3K36me3 and RNA Polymerase II activity compared to its wild type variants. This report paves the way for further studies involving epigenetic regulation in laminopathies which would be an important step in explaining the molecular mechanism and pathophysiology of the diseases like dilated cardiomyopathy. High LightsO_LIlamin A K97E mutation predominantly alters H3K9me3 histone modifications landscape C_LIO_LIlamin A K97E aggregates within nucleus also sequester the HP1{gamma} C_LIO_LIlamin A K97E mutation affects RNA polymerase II distribution pattern C_LI