title: Promoter methylation of yes-associated protein (YAP1) gene in polycystic ovary syndrome.
abstract: BACKGROUND
  DNA methylation modification has been proved to influence the phenotype of polycystic ovary syndrome (PCOS). Genome-wide association studies (GWAS) demonstrate that yes-associated protein (YAP1) genetic sites are associated with PCOS. The study aims to detect the methylation status of YAP1 promoter in ovary granulosa cells (GCs) of PCOS patients and explore novel therapeutic targets for PCOS.
  
  
  METHODS
  Randomized controlled trial was applied and a total of 72 women were included in the study, including 36 cases of PCOS patients and 36 cases of health controls. Ovary GCs were extracted from in vitro fertilization embryo transfer. Methylation status of YAP1 promoter was detected by bisulfite sequencing PCR (BSP). Protein and mRNA expression of YAP1 were measured by western blotting and real-time quantitate PCR.
  
  
  RESULTS
  Overall methylation level of YAP1 promoter region from PCOS group was significantly lower than that from control group. CpG sites analysis revealed that 12 sites (-443, -431, -403, -371, -331, -120, -49, -5, +1, +9, +15, +22) were significantly hypomethylated in women with PCOS (P < 0.05). A significant upregulation of YAP1 mRNA and protein expression levels was observed. Testosterone concentration could alleviate the methylation status and demonstrate obvious dose-dependent relation.
  
  
  CONCLUSIONS
  Our research achievements manifest that hypomethylation of YAP1 promoter promotes the YAP1 expression, which plays a key role in the pathogenesis and accelerate PCOS.
authors.affiliation: aSecond Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan Province bZhengzhou University, Zhengzhou, Henan Province cReproductive Medical Center, People's Hospital of Henan Province, Zhengzhou, Henan Province, P.R. China.
authors.forename: Li-Le
authors.initials: LL
authors.lastname: Jiang
authors.forename: Juan-Ke
authors.initials: JK
authors.lastname: Xie
authors.forename: Jin-Quan
authors.initials: JQ
authors.lastname: Cui
authors.forename: Duo
authors.initials: D
authors.lastname: Wei
authors.forename: Bao-Li
authors.initials: BL
authors.lastname: Yin
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Zhang
authors.forename: Yuan-Hui
authors.initials: YH
authors.lastname: Chen
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Cui-Lian
authors.initials: CL
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D005640:Follicle Stimulating Hormone; D006107:Granulosa Cells / Q000378:metabolism; D006801:Humans; D007986:Luteinizing Hormone; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013739:Testosterone; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone