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• W3090379712 abstract "The pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone, signal the gonads to regulate male and female fertility. FSH is critical for female fertility as it regulates oocyte maturation, ovulation, and hormone synthesis. Multiple genome-wide association studies (GWAS) link a 130 Kb locus at 11p14.1, which encompasses the FSH beta-subunit (FSHB) gene, with fertility-related traits that include polycystic ovary syndrome, age of natural menopause, and dizygotic twinning. The most statistically significant single nucleotide polymorphism from several GWAS studies (rs11031006) resides within a highly conserved 450 bp region 26 Kb upstream of the human FSHB gene. Given that sequence conservation suggests an important biological function, we hypothesized that the region could regulate FSHB transcription. In luciferase assays, the conserved region enhanced FSHB transcription and gel shifts identified a binding site for Steroidogenic factor 1 (SF1) contributing to its function. Analysis of mouse pituitary single-cell ATAC-seq demonstrated open chromatin at the conserved region exclusive to a gonadotrope cell-type cluster. Additionally, enhancer-associated histone markers were identified by immunoprecipitation of chromatin from mouse whole pituitary and an immortalized mouse gonadotrope-derived LβT2 cell line at the conserved region. Furthermore, we found that the rs11031006 minor allele upregulated FSHB transcription via increased SF1 binding to the enhancer. All together, these results identify a novel upstream regulator of FSHB transcription and indicate that rs11031006 can modulate FSH levels." @default.
• W3090379712 created "2020-10-08" @default.
• W3090379712 creator A5001513312 @default.
• W3090379712 creator A5039735928 @default.
• W3090379712 creator A5042178162 @default.
• W3090379712 creator A5050968979 @default.
• W3090379712 creator A5059152505 @default.
• W3090379712 date "2020-10-03" @default.
• W3090379712 modified "2023-10-17" @default.
• W3090379712 title "<i>FSHB</i> Transcription is Regulated by a Novel 5′ Distal Enhancer With a Fertility-Associated Single Nucleotide Polymorphism" @default.
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• W3090379712 doi "https://doi.org/10.1210/endocr/bqaa181" @default.
• W3090379712 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7846141" @default.
• W3090379712 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33009549" @default.
• W3090379712 hasPublicationYear "2020" @default.

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