Progetto di ricerca

AFM-21030 (DSB.AD007.149)

Area tematica

Scienze biomediche

Area progettuale

Biomedicina Traslazionale (DSB.AD007)

Struttura responsabile del progetto di ricerca

Istituto di Biochimica e Biologia Cellulare (IBBC)

Altre strutture che collaborano al progetto di ricerca

Responsabile di progetto

Telefono: 0690091307


The most common group of Lamin A/C-associated diseases are the muscular dystrophies such as Emery Dreifuss Muscular Dystrophy (EDMD). Although the penetrance of EDMD varies a lot among patients, suggesting an involvement of the individual epigenetic background to the disease is still unclear which is the epigenetic role of Lamin A/C in the aberrant muscle differentiation observed in EDMD. We propose a model of nuclear architecture depicting Lamin A/C as determinant of gene expression regulation throughout the interplay with specific epigenetic regulators. In our recent work we described a clear interplay between Lamin A/C and key epigenetic repressors, the Polycomb group (PcG) of proteins. We have shown that,at the onset myogenesis, a fine regulation of this crosstalk, by controlling the timing of muscle-specific gene activation, ensures a correct muscle differentiation. With this project we propose to describe how PcG repressors may contribute to the EDMD pathogenesis and progression.


The long-term goal of our research is the identification of therapeutically relevant early-stage epigenetic alterations in EDMD pathogenesis and the definition of their interplay in disease progression. This will be achieved using two mouse models of EDMD and innovative techniques, based on high-throughput DNA sequencing to fulfill the following aims: 1. Evaluating muscle regeneration in the EDMD H222P mouse model 2. Dissection of the functional contribution of PcG proteins and chromatin compartmentalization in EDMD pathology 3. Tissue-specific analysis of senescence programs in EDMD patients-derived cells. The novelty of our project is a new approach to EDMD research that will explore the epigenetic aspect of lamin function during different stages of dystrophy development, providing a full understanding of EDMD pathogenesis and progression as an evolving complex system. If successful this proposal will give a massive output to progress in elucidating relevance of epigenetic factors in regulating satellite stem cell niche, and the contribution of their dysfunctions, imposed by pathological conditions (Lmna mutation), to EDMD pathology. The identification of epigenetic defects that

Data inizio attività


Parole chiave

epigenetica, chromatin conformation, emery dreifuss muscular dystrophy

Ultimo aggiornamento: 30/11/2023