MyoD induces ARTD1 and nucleoplasmic poly-ADP-ribosylation during fibroblast to myoblast transdifferentiation
Lavinia Bisceglie,
Ann-Katrin Hopp,
Kapila Gunasekera,
Roni H. Wright,
François Le Dily,
Enrique Vidal,
Alessandra Dall’Agnese,
Luca Caputo,
Chiara Nicoletti,
Pier Lorenzo Puri,
Miguel Beato,
Michael O. Hottiger
Affiliations
Lavinia Bisceglie
Department of Molecular Mechanisms of Disease, University of Zurich, Zurich, Switzerland; Molecular Life Science PhD Program of the Life Science Zurich Graduate School, University of Zurich, Zurich, Switzerland
Ann-Katrin Hopp
Department of Molecular Mechanisms of Disease, University of Zurich, Zurich, Switzerland
Kapila Gunasekera
Department of Molecular Mechanisms of Disease, University of Zurich, Zurich, Switzerland
Roni H. Wright
Centre de Regulació Genomica (CRG), Barcelona Institute of Science and Technology (BIST), Dr. Aiguader 88, 08003 Barcelona, Spain; Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya (UIC), 08003 Barcelona, Spain
François Le Dily
Centre de Regulació Genomica (CRG), Barcelona Institute of Science and Technology (BIST), Dr. Aiguader 88, 08003 Barcelona, Spain
Enrique Vidal
Centre de Regulació Genomica (CRG), Barcelona Institute of Science and Technology (BIST), Dr. Aiguader 88, 08003 Barcelona, Spain
Alessandra Dall’Agnese
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA
Luca Caputo
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA
Chiara Nicoletti
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA
Pier Lorenzo Puri
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA
Miguel Beato
Centre de Regulació Genomica (CRG), Barcelona Institute of Science and Technology (BIST), Dr. Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain
Michael O. Hottiger
Department of Molecular Mechanisms of Disease, University of Zurich, Zurich, Switzerland; Corresponding author
Summary: While protein ADP-ribosylation was reported to regulate differentiation and dedifferentiation, it has so far not been studied during transdifferentiation. Here, we found that MyoD-induced transdifferentiation of fibroblasts to myoblasts promotes the expression of the ADP-ribosyltransferase ARTD1. Comprehensive analysis of the genome architecture by Hi-C and RNA-seq analysis during transdifferentiation indicated that ARTD1 locally contributed to A/B compartmentalization and coregulated a subset of MyoD target genes that were however not sufficient to alter transdifferentiation. Surprisingly, the expression of ARTD1 was accompanied by the continuous synthesis of nuclear ADP ribosylation that was neither dependent on the cell cycle nor induced by DNA damage. Conversely to the H2O2-induced ADP-ribosylation, the MyoD-dependent ADP-ribosylation was not associated to chromatin but rather localized to the nucleoplasm. Together, these data describe a MyoD-induced nucleoplasmic ADP-ribosylation that is observed particularly during transdifferentiation and thus potentially expands the plethora of cellular processes associated with ADP-ribosylation.
