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A novel intergenic enhancer that regulates Bdnf expression in developing cortical neurons

Brookes, E; Martinez De La Cruz, B; Boulasiki, P; Au, HYA; Varsally, W; Barrington, C; Hadjur, S; (2023) A novel intergenic enhancer that regulates Bdnf expression in developing cortical neurons. iScience , 26 (1) , Article 105695. 10.1016/j.isci.2022.105695. Green open access

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Abstract

Brain-derived neurotrophic factor (BDNF) promotes neuronal differentiation and survival and is implicated in the pathogenesis of many neurological disorders. Here, we identified a novel intergenic enhancer located 170 kb from the Bdnf gene, which promotes the expression of Bdnf transcript variants during mouse neuronal differentiation and activity. Following Bdnf activation, enhancer-promoter contacts increase, and the region moves away from the repressive nuclear periphery. Bdnf enhancer activity is necessary for neuronal clustering and dendritogenesis in vitro, and for cortical development in vivo. Our findings provide the first evidence of a regulatory mechanism whereby the activation of a distal enhancer promotes Bdnf expression during brain development.

Type: Article
Title: A novel intergenic enhancer that regulates Bdnf expression in developing cortical neurons
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.isci.2022.105695
Publisher version: https://doi.org/10.1016/j.isci.2022.105695
Language: English
Additional information: ©2022. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Biological sciences, Developmental neuroscience, Molecular neuroscience, Neuroscience
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 Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10162599
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