biostudies-literatureUnknown10(2)Griffin ENTranscription factors play vital roles in neuron development; however, little is known about the role of these proteins in maintaining neuronal homeostasis. Here, we show that the transcription factor RREB1 (Ras-responsive element-binding protein 1) is essential for neuron survival in the mammalian brain. A spontaneous mouse mutation causing loss of a nervous system-enriched Rreb1 transcript is associated with progressive loss of cerebellar Purkinje cells and ataxia. Analysis of chromatin immunoprecipitation and sequencing, along with RNA sequencing data revealed dysregulation of RREB1 targets associated with the microtubule cytoskeleton. In agreement with the known role of microtubules in dendritic development, dendritic complexity was disrupted in Rreb1-deficient neurons. AScience advanceseadh3929https://www.ebi.ac.uk/biostudies/studies/S-EPMC10780896biostudies-literatureRREB1 regulates neuronal proteostasis and the microtubule network.PMC10780896Sim SEGriffin ENHarris BSAckerman SLJucius THeinz SfalseRREB1 regulates neuronal proteostasis and the microtubule network.Transcription factors play vital roles in neuron development; however, little is known about the role of these proteins in maintaining neuronal homeostasis. Here, we show that the transcription factor RREB1 (Ras-responsive element-binding protein 1) is essential for neuron survival in the mammalian brain. A spontaneous mouse mutation causing loss of a nervous system-enriched Rreb1 transcript is associated with progressive loss of cerebellar Purkinje cells and ataxia. Analysis of chromatin immunoprecipitation and sequencing, along with RNA sequencing data revealed dysregulation of RREB1 targets associated with the microtubule cytoskeleton. In agreement with the known role of microtubules in dendritic development, dendritic complexity was disrupted in Rreb1-deficient neurons. A2024-01-01T00:00:00Z2024 Jan2025-04-22T10:41:25.222Z2025-04-05T23:40:01.765ZS-EPMC107808963819853810.1126/sciadv.adh3929