Investigating the impact of the lamina-associated TDark network on chromatin architecture dysfunction in Emery-Dreifuss Muscular Dystrophy

This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2025.

Emery-Dreifuss Muscular Dystrophy (EDMD) is a rare genetic disorder that weakens muscles, including the heart. It is caused by mutations in genes that help maintain the structure of the cell nucleus. Even though different mutations can lead to EDMD, they all cause problems in how skeletal and heart muscles function. Research studies in this field, including our own, has shown that these mutations disrupt the nucleus's shape and organization, leading to changes in how genes are read and regulated. In a previous study, we explored a protein called MLIP, which plays a role in muscle development. When MLIP was missing, several genes behaved abnormally, including NEMP1 and SERTAD4, which belong to the "TDark" category, of proteins with function not well understood. Since these genes may be linked to EDMD, we believe they could be part of a larger network of proteins that influence how genes function in muscle cells. In this project, we aim to study how NEMP1 and SERTAD4 affect gene activity and muscle cell development, and to understand how they may contribute to EDMD pathological phenotype. To do this, we will use cutting-edge molecular biology techniques, including innovative methods developed by our laboratories (SAMMY-seq and 4f-SAMMY-seq), to analyze how the 3D structure of the genome is affected. By understanding the roles of NEMP1 and SERTAD4, our research could reveal new insights into how muscle differentiation is regulated at the molecular and cellular level. This knowledge may eventually help scientists develop treatments to slow or stop the progression of EDMD.