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


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.

SUBMITTER: Brookes E 

PROVIDER: S-EPMC9792897 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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A novel intergenic enhancer that regulates <i>Bdnf</i> expression in developing cortical neurons.

Brookes Emily E   Martinez De La Cruz Braulio B   Boulasiki Paraskevi P   Au Ho Yu Alan HYA   Varsally Wazeer W   Barrington Christopher C   Hadjur Suzana S   Riccio Antonella A  

iScience 20221201 1


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 <i>Bdnf</i> gene, which promotes the expression of <i>Bdnf</i> transcript variants during mouse neuronal differentiation and activity. Following <i>Bdnf</i> activation, enhancer-promoter contacts increase, and the region moves away from the repressive nuclear periphery.  ...[more]

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