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

doi:10.1016/j.isci.2021.102432

MyoD induces ARTD1 and nucleoplasmic poly-ADP-ribosylation during fibroblast to myoblast transdifferentiation

iScience. 2021 Apr 17;24(5):102432. doi: 10.1016/j.isci.2021.102432. eCollection 2021 May 21.

Authors

Affiliations

¹ Department of Molecular Mechanisms of Disease, University of Zurich, Zurich, Switzerland.
² Molecular Life Science PhD Program of the Life Science Zurich Graduate School, University of Zurich, Zurich, Switzerland.
³ Centre de Regulació Genomica (CRG), Barcelona Institute of Science and Technology (BIST), Dr. Aiguader 88, 08003 Barcelona, Spain.
⁴ Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya (UIC), 08003 Barcelona, Spain.
⁵ Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
⁶ Universitat Pompeu Fabra (UPF), Barcelona, Spain.

Abstract

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.

Keywords: Biological Sciences; Cell Biology; Developmental Biology; Molecular Biology.

Grants and funding

R01 GM134712/GM/NIGMS NIH HHS/United States