title: Growth Cone Localization of the mRNA Encoding the Chromatin Regulator HMGN5 Modulates Neurite Outgrowth.
abstract: Neurons exploit local mRNA translation and retrograde transport of transcription factors to regulate gene expression in response to signaling events at distal neuronal ends. Whether epigenetic factors could also be involved in such regulation is not known. We report that the mRNA encoding the high-mobility group N5 (HMGN5) chromatin binding protein localizes to growth cones of both neuron-like cells and of hippocampal neurons, where it has the potential to be translated, and that HMGN5 can be retrogradely transported into the nucleus along neurites. Loss of HMGN5 function induces transcriptional changes and impairs neurite outgrowth, while HMGN5 overexpression induces neurite outgrowth and chromatin decompaction; these effects are dependent on growth cone localization of Hmgn5 mRNA. We suggest that the localization and local translation of transcripts coding for epigenetic factors couple the dynamic neuronal outgrowth process with chromatin regulation in the nucleus.
authors.affiliation: Cell Migration and Neuritogenesis, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Francesca
authors.initials: F
authors.lastname: Moretti
authors.affiliation: Embryology and Stem Cell Biology, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Chiara
authors.initials: C
authors.lastname: Rolando
authors.affiliation: Cell Migration and Neuritogenesis, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Moritz
authors.initials: M
authors.lastname: Winker
authors.affiliation: Bioinformatics, Department of Biomedicine, University of Basel, Basel, Switzerland Swiss Institute of Bioinformatics, Basel, Switzerland.
authors.forename: Robert
authors.initials: R
authors.lastname: Ivanek
authors.affiliation: System Biology Ireland-Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Javier
authors.initials: J
authors.lastname: Rodriguez
authors.affiliation: System Biology Ireland-Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Alex
authors.initials: A
authors.lastname: Von Kriegsheim
authors.affiliation: Embryology and Stem Cell Biology, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Verdon
authors.initials: V
authors.lastname: Taylor
authors.affiliation: Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bustin
authors.affiliation: Cell Migration and Neuritogenesis, Department of Biomedicine, University of Basel, Basel, Switzerland olivier.pertz@unibas.ch.
authors.forename: Olivier
authors.initials: O
authors.lastname: Pertz
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D020439:Growth Cones / Q000378:metabolism*; D024001:HMGN Proteins / Q000235:genetics*; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D002843:Chromatin; D024001:HMGN Proteins; C498963:Hmgn5 protein, mouse; D012333:RNA, Messenger
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