Three-Dimensional Genome Interactions Identify Potential Adipocyte Metabolism-Associated Gene STON1 and Immune-Correlated Gene FSHR at the rs13405728 Locus in Polycystic Ovary Syndrome

Autor: Can-hui Cao, Ye Wei, Rang Liu, Xin-ran Lin, Jia-qi Luo, Qiu-ju Zhang, Shou-ren Lin, Lan Geng, Si-kang Ye, Yu Shi, Xi Xia
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Frontiers in Endocrinology, Vol 12 (2021)
Druh dokumentu: article
ISSN: 1664-2392
DOI: 10.3389/fendo.2021.686054
Popis: Backgroundrs13405728 was identified as one of the most prevalent susceptibility loci for polycystic ovary syndrome (PCOS) in Han Chinese and Caucasian women. However, the target genes and potential mechanisms of the rs13405728 locus remain to be determined.MethodsThree-dimensional (3D) genome interactions from the ovary tissue were characterized via high-through chromosome conformation capture (Hi-C) and Capture Hi-C technologies to identify putative targets at the rs13405728 locus. Combined analyses of eQTL, RNA-Seq, DNase-Seq, ChIP-Seq, and sing-cell sequencing were performed to explore the molecular roles of these target genes in PCOS. PCOS-like mice were applied to verify the expression patterns.ResultsGenerally, STON1 and FSHR were identified as potential targets of the rs13405728 locus in 3D genomic interactions with epigenomic regulatory peaks, with STON1 (P=0.0423) and FSHR (P=0.0013) being highly expressed in PCOS patients. STON1 co-expressed genes were associated with metabolic processes (P=0.0008) in adipocytes (P=0.0001), which was validated in the fat tissue (P
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