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Gestational choline supplementation improves cross-generational mood by epigenetic upregulation of Nr3c1

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE84317 | GEO | 2021/09/01

REPOSITORIES: GEO

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Gestational choline supplementation improves cross-generational mood by epigenetic upregulation of Nr3c1 [RRBS]

Project description:Environmental cues during gestation could exert transgenerational effects on behavior mainly through changes in epigenetic marks such as DNA methylation. However, the role of histone modifications in the inheritance of acquired phenotypes remains largely unknown in mammals. Here, we report that gestational choline supplementation (GCS) in maternal mice exerts anxiolytic effects on male offspring across 2 generations. Correspondingly, GCS-induced H3K9 hyperacetylation in the Nr3c1 promoter in male hippocampus leads to upregulation of Nr3c1 and its encoded protein, glucocorticoid receptor (GR), across 2 generations through the male germline. Furthermore, inhibition of CREB-binding protein (CBP) histone acetyltransferase (HAT) function restored GCS-induced epigenetic and behavioral alterations, suggesting that CBP function as a HAT to increase Nr3c1 expression through H3K9 hyperacetylation. Thus, GCS-induced GR upregulation through CBP-mediated H3K9 hyperacetylation in the Nr3c1 promoter is associated with anxiolytic behavior in male offspring, highlighting the role of histone modification in acquired phenotypes across mammalian generations.

2021-09-01 | GSE84316 | GEO