A novel intergenic enhancer that regulates Bdnf expression in developing cortical neurons
A novel intergenic enhancer that regulates Bdnf expression in developing cortical neurons
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.
Brookes, Emily
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Martinez De La Cruz, Braulio
ac2d2a18-6b90-45cf-a46e-205974aea3c7
Boulasiki, Paraskevi
75e382cd-07e3-4136-bb5c-8c46895965c1
Au, Ho Yu Alan
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Varsally, Wazeer
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Barrington, Christopher
ac5f380d-91fe-48c9-8e8c-4a483d0cd670
Hadjur, Suzana
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Riccio, Antonella
978b3e6e-124d-4709-bd00-43bb0a936a44
17 December 2022
Brookes, Emily
425dafc2-111b-4f6c-9336-f720c4ef8cac
Martinez De La Cruz, Braulio
ac2d2a18-6b90-45cf-a46e-205974aea3c7
Boulasiki, Paraskevi
75e382cd-07e3-4136-bb5c-8c46895965c1
Au, Ho Yu Alan
0ce3b408-6131-46f3-ac64-6a1de858ee44
Varsally, Wazeer
ae26a746-30c7-4e96-81c0-75f77799580c
Barrington, Christopher
ac5f380d-91fe-48c9-8e8c-4a483d0cd670
Hadjur, Suzana
3fe89885-b9f7-453d-9aaf-4c18d22b3c95
Riccio, Antonella
978b3e6e-124d-4709-bd00-43bb0a936a44
Brookes, Emily, Martinez De La Cruz, Braulio, Boulasiki, Paraskevi, Au, Ho Yu Alan, Varsally, Wazeer, Barrington, Christopher, Hadjur, Suzana and Riccio, Antonella
(2022)
A novel intergenic enhancer that regulates Bdnf expression in developing cortical neurons.
iScience, 26 (1).
(doi:10.1016/j.isci.2022.105695).
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.
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Accepted/In Press date: 24 November 2022
e-pub ahead of print date: 1 December 2022
Published date: 17 December 2022
Identifiers
Local EPrints ID: 474269
URI: http://eprints.soton.ac.uk/id/eprint/474269
ISSN: 2589-0042
PURE UUID: 6b05b0b4-d1e0-4fff-8647-5d1025b7707c
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Date deposited: 16 Feb 2023 18:08
Last modified: 17 Mar 2024 04:14
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Contributors
Author:
Emily Brookes
Author:
Braulio Martinez De La Cruz
Author:
Paraskevi Boulasiki
Author:
Ho Yu Alan Au
Author:
Wazeer Varsally
Author:
Christopher Barrington
Author:
Suzana Hadjur
Author:
Antonella Riccio
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