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Epigenetic control of adaptive or homeostatic splicing during interval-training activities.


ABSTRACT: Interval-training activities induce adaptive cellular changes without altering their fundamental identity, but the precise underlying molecular mechanisms are not fully understood. In this study, we demonstrate that interval-training depolarization (ITD) of pituitary cells triggers distinct adaptive or homeostatic splicing responses of alternative exons. This occurs while preserving the steady-state expression of the Prolactin and other hormone genes. The nature of these splicing responses depends on the exon's DNA methylation status, the methyl-C-binding protein MeCP2 and its associated CA-rich motif-binding hnRNP L. Interestingly, the steady expression of the Prolactin gene is also reliant on MeCP2, whose disruption leads to exacerbated multi-exon aberrant splicing and overexpression of the hormone gene transcripts upon ITD, similar to the observed hyperprolactinemia or activity-dependent aberrant splicing in Rett Syndrome. Therefore, epigenetic control is crucial for both adaptive and homeostatic splicing and particularly the steady expression of the Prolactin hormone gene during ITD. Disruption in this regulation may have significant implications for the development of progressive diseases.

SUBMITTER: Liu L 

PROVIDER: S-EPMC11229381 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Epigenetic control of adaptive or homeostatic splicing during interval-training activities.

Liu Ling L   Nguyen Hai H   Das Urmi U   Ogunsola Samuel S   Yu Jiankun J   Lei Lei L   Kung Matthew M   Pejhan Shervin S   Rastegar Mojgan M   Xie Jiuyong J  

Nucleic acids research 20240701 12


Interval-training activities induce adaptive cellular changes without altering their fundamental identity, but the precise underlying molecular mechanisms are not fully understood. In this study, we demonstrate that interval-training depolarization (ITD) of pituitary cells triggers distinct adaptive or homeostatic splicing responses of alternative exons. This occurs while preserving the steady-state expression of the Prolactin and other hormone genes. The nature of these splicing responses depen  ...[more]

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