English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  rs13405728 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.    Methods  Three-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.    Results  Generally,  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 <0.0001) and ovary ( P =0.0035) from fat-diet mice. The immune system process (GO:0002376) was enriched in  FSHR  co-expressed genes ( P =0.0002) and PCOS patients ( P =0.0002), with  CD4  high expression in PCOS patients ( P =0.0316) and PCOS-like models ( P =0.0079). Meanwhile,  FSHR  expression was positively correlated with  CD4  expression in PCOS patients (P=0.0252) and PCOS-like models ( P =0.0178). Furthermore, androgen receptor ( AR ) was identified as the common transcription factor for  STON1  and  FSHR  and positively correlated with the expression of  STON1  ( P =0.039) and  FSHR  ( P =4e-06) in ovary tissues and PCOS-like mice.    Conclusion  Overall, we identified  STON1  and  FSHR  as potential targets for the rs13405728 locus and their roles in the processes of adipocyte metabolism and  CD4  immune expression in PCOS, which provides 3D genomic insight into the pathogenesis of PCOS.

frontiers in endocrinology

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