Targeting Nr2e3 to Modulate Tet2 Expression: Therapeutic Potential for Depression Treatment.

ABSTRACT: Epigenetic mechanisms such as DNA methylation and hydroxymethylation play a significant role in depression. This research has shown that Ten-eleven translocation 2 (Tet2) deficiency prompts depression-like behaviors, but Tet2's transcriptional regulation remains unclear. In the study, bioinformatics is used to identify nuclear receptor subfamily 2 group E member 3 (Nr2e3) as a potential Tet2 regulator. Nr2e3 is found to enhance Tet2's transcriptional activity by binding to its promoter region. Nr2e3 knockdown in mouse hippocampus leads to reduced Tet2 expression, depression-like behaviors, decreased hydroxymethylation of synaptic genes, and downregulation of synaptic proteins like postsynaptic density 95 KDa (PSD95) and N-methy-d-aspartate receptor 1 (NMDAR1). Fewer dendritic spines are al

SUBMITTER: Ma X 

PROVIDER: S-EPMC11336902 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature