Proteomic analysis reveals Utf1 as a neurogenesis-associated new Sumo target

Abstract

Post-translational modification by covalent attachment of Sumo regulates numerous processes in vertebrates. Despite demonstrated roles of Sumo in development and function of the nervous system, the identification of key factors displaying a sumoylation-dependent activity during neurogenesis remains elusive. Based on SILAC, we have identified the Sumo proteome of proliferating and neuronal-differentiating cells. More than 300 putative Sumo targets differentially associated with one or the other condition. Among these, Utf1 revealed as a new Sumo target. Gain-of-function experiments demonstrated marked differences between the effects on neurogenesis of wild type and sumoylation mutant versions of selected proteins. While sumoylation of Prox1, Sall4a, Trim24 and Utf1 associated with a positive effect on neurogenesis, sumoylation of Kctd15 associated with a negative effect. Similar results were observed in embryos. Finally, detailed analysis of Utf1 showed sumoylation-dependent control of bivalent genes expression. This effect relies on two mechanisms: sumoylation modulates Utf1 chromatin binding and mediates recruitment of the mRNA-decapping enzyme Dcp1a through a conserved SIM. Altogether, our results indicate that combined sumoylation status of key proteins determine proper progress of neurogenesis. Sumo/transcription/chromatin/neurogenesis/Utf1