Mechanotransduction, nuclear architecture and epigenetics in Emery Dreifuss Muscular Dystrophy: tous pour un, un pour tous

Nucleus. 2018 Jan 1;9(1):276-290. doi: 10.1080/19491034.2018.1460044.


The alteration of the several roles that Lamin A/C plays in the mammalian cell leads to a broad spectrum of pathologies that - all together - are named laminopathies. Among those, the Emery Dreifuss Muscular Dystrophy (EDMD) is of particular interest as, despite the several known mutations of Lamin A/C, the genotype-phenotype correlation still remains poorly understood; this suggests that the epigenetic background of patients might play an important role during the time course of the disease. Historically, both a mechanical role of Lamin A/C and a regulative one have been suggested as the driving force of laminopathies; however, those two hypotheses are not mutually exclusive. Recent scientific evidence shows that Lamin A/C sustains the correct gene expression at the epigenetic level thanks to the Lamina Associated Domains (LADs) reorganization and the crosstalk with the Polycomb Group of Proteins (PcG). Furthermore, the PcG-dependent histone mark H3K27me3 increases under mechanical stress, finally pointing out the link between the mechano-properties of the nuclear lamina and epigenetics. Here, we summarize the emerging mechanisms that could explain the high variability seen in Emery Dreifuss muscular dystrophy.

Keywords: Emery Dreifuss Muscular Dystrophy; Epigenetics; Lamin A/Cmechanotrasduction; nuclear architecture; transcription.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Nucleus / genetics*
  • Cell Nucleus / metabolism
  • Epigenesis, Genetic*
  • Humans
  • Mechanotransduction, Cellular / genetics*
  • Muscular Dystrophy, Emery-Dreifuss / genetics*
  • Muscular Dystrophy, Emery-Dreifuss / metabolism

Grants and funding

flagship CNR projects (Epigen), My First AIRC Grant (18535), the Italian Minister of Health (GR-2013-02355413), AFM-Téléthon (FR) (21030), flagship CNR projects (Interomics), Italian Ministry of Research and University (RBFR106S1Z_001).