MyoD induces ARTD1-dependent nuclear ADP-ribosylation during fibroblasts to myoblasts trans-differentiation

Trans-differentiation is the conversion of a differentiated somatic cell type into another one without de-differentiation and re-acquisition of the pluripotent state. Several studies suggested a role of ADP-ribosylation in regulating chromatin changes associated with differentiation and de-differentiation processes, but the role of ADP-ribosylation in cell-type conversion is unknown.MyoD is a master transcription factor, whose expression is sufficient to trans-differentiate fibroblasts to myoblasts. We observed a MyoD-dependent enhanced expression of ARTD1 that co-regulated only a subset of MyoD target genes in fibroblast-derived myoblasts. Comprehensive analysis of the genome organization by Hi-C analysis suggested that ARTD1 and ARTD1-dependent ADP-ribosylation might contribute to A/B compartmentalization in IMR90 cells, but not in a MyoD-dependent manner. The induction of ARTD1 was accompanied by the synthesis of nuclear ADP-ribosylation that was neither dependent on the cell cycle nor on DNA damage or transcriptional elongation. However, MyoD-induced trans-differentiation increased the DNA damage response induced by etoposide. Together, these data provide further insights into the molecular mechanisms associated with cell type conversion and nuclear ADP-ribosylation.