MLL4 protein tunes chromatin compaction and regulates nuclear mechanical stress

Recent evidences show the growing importance of mechanical forces in directing basic processes in cellular functions through the complex scenario of mechanotransduction. In this context, however, the impact of chromatin physical state on cellular structure and function requires further study. Here, we characterized the effects of a loss-of-function mutation of MLL4, a chromatin regulator, on nuclear mechanical and structural properties. Measurements of such features in intact cells are to date challenging, as current gold-standard methods for mechanobiology cannot have access to subcellular structures: a complete characterization of their nuclear mechanical fingerprint is hence still elusive. By exploiting the innovative all-optical technique of Brillouin microscopy in our custom-made optical setup, we measured with three-dimensional sub-micrometric resolution the effects of MLL4-dependent mechanical stress on the nucleus of mesenchymal stem cells in different conditions. These results show the importance of mechanotransduction for vital cellular processes and pave the way towards the use of Brillouin microscopy as a reliable tool for medical diagnostic purposes of chromatinopathies, this mutation being involved in Kabuki syndrome, a severe genetic disease.