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NuRD-independent Mi-2 activity represses ectopic gene expression during neuronal maturation

Aughey, GN; Forsberg, E; Grimes, K; Zhang, S; Southall, TD; (2023) NuRD-independent Mi-2 activity represses ectopic gene expression during neuronal maturation. EMBO Reports , Article e55362. 10.15252/embr.202255362. Green open access

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Abstract

During neuronal development, extensive changes to chromatin states occur to regulate lineage-specific gene expression. The molecular factors underlying the repression of non-neuronal genes in differentiated neurons are poorly characterised. The Mi2/NuRD complex is a multiprotein complex with nucleosome remodelling and histone deacetylase activity. Whilst NuRD has previously been implicated in the development of nervous system tissues, the precise nature of the gene expression programmes that it coordinates is ill-defined. Furthermore, evidence from several species suggests that Mi-2 may be incorporated into multiple complexes that may not possess histone deacetylase activity. We show that Mi-2 activity is required for suppressing ectopic expression of germline genes in neurons independently of HDAC1/NuRD, whilst components of NuRD, including Mi-2, regulate neural gene expression to ensure proper development of the larval nervous system. We find that Mi-2 binding in the genome is dynamic during neuronal maturation, and Mi-2-mediated repression of ectopic gene expression is restricted to the early stages of neuronal development, indicating that Mi-2/NuRD is required for establishing stable neuronal transcriptomes during the early stages of neuronal differentiation.

Type: Article
Title: NuRD-independent Mi-2 activity represses ectopic gene expression during neuronal maturation
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.15252/embr.202255362
Publisher version: https://doi.org/10.15252/embr.202255362
Language: English
Additional information: © 2023 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Drosophila, NuRD, chromatin, differentiation, neurons
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
URI: https://discovery.ucl.ac.uk/id/eprint/10164985
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