Growth cone localization of the mRNA encoding the chromatin regulator HMGN5 modulates neurite outgrowth

Neurons exploit local mRNAtranslation 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.Wereport that themRNAencoding the high-mobility group N5 (HMGN5) chromatin binding protein localizes to growth cones of both neuronlike cells and of hippocampal neurons, where it has the potential to be translated, and thatHMGN5can be retrogradely transported into the nucleus along neurites. Loss ofHMGN5function induces transcriptional changes and impairs neurite outgrowth, while HMGN5overexpression induces neurite outgrowth and chromatin decompaction; these effects are dependent on growth cone localization of Hmgn5 mRNA.Wesuggest that the localization and local translation of transcripts coding for epigenetic factors couple the dynamic neuronal outgrowth process with chromatin regulation in the nucleus.