title: Naturally occurring genetic mutations in the 5'-upstream regulatory region of bovine FSHB generate a novel cis-regulatory element that affects its expression.
abstract: We previously reported that numerous naturally occurring genetic mutations in the 5'-upstream regulatory region (5'-URR) of the bovine follicle-stimulating hormone beta-subunit gene (FSHB) were associated with reduced serum follicle-stimulating hormone (FSH) levels, poor-quality semen and low fertility in bulls. In addition, two different FSHB mRNA transcripts resulting from the linked mutations of genomic DNA were discovered in mutation-bearing bull pituitaries. Here, using electrophoretic mobility shift assay, we identified c.-1539_-1538delGGinsTTAACT mutations in the 5'-URR that generated a novel cis-regulatory element in bovine FSHB. Moreover, this novel element seemed to play a role in repressing FSHB transcription based on a promoter activity analysis in LβT2 gonadotrope cells. Quantitative assays of FSHB mRNA in the bovine pituitaries suggested that the levels of FSHB wild-type transcripts in the mutation-bearing bulls were significantly lower (P < 0.05) than in those of bulls without FSHB genetic mutations and that the levels of FSHB-mutated transcripts were significantly lower (P < 0.05) than that of wild-type transcripts in the mutation-bearing bulls. Altogether, our results suggest that decreased serum FSH levels and male fertility in bulls with the c.-1539_-1538delGGinsTTAACT mutation likely result from the alteration of cis-regulatory elements and induction of FSHB transcription.
authors.affiliation: Laboratory Animal Center, College of Animal Sciences, Jilin University, Changchun, China.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Dai
authors.affiliation: Laboratory Animal Center, College of Animal Sciences, Jilin University, Changchun, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Laboratory Animal Center, College of Animal Sciences, Jilin University, Changchun, China.
authors.forename: Wangyang
authors.initials: W
authors.lastname: Yu
authors.affiliation: Laboratory Animal Center, College of Animal Sciences, Jilin University, Changchun, China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Laboratory Animal Center, College of Animal Sciences, Jilin University, Changchun, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Laboratory Animal Center, College of Animal Sciences, Jilin University, Changchun, China.
authors.forename: Lianjiang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Laboratory Animal Center, College of Animal Sciences, Jilin University, Changchun, China.
authors.forename: Bao
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Laboratory Animal Center, College of Animal Sciences, Jilin University, Changchun, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Laboratory Animal Center, College of Animal Sciences, Jilin University, Changchun, China.
authors.forename: Tenghe
authors.initials: T
authors.lastname: Ma
authors.affiliation: Laboratory Animal Center, College of Animal Sciences, Jilin University, Changchun, China.
authors.forename: Jiabao
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002417:Cattle / Q000235:genetics*; D004252:DNA Mutational Analysis; D024202:Electrophoretic Mobility Shift Assay; D037201:Follicle Stimulating Hormone, beta Subunit / Q000235:genetics*; D005786:Gene Expression Regulation; D007248:Infertility, Male / Q000235:genetics; D008297:Male; D009154:Mutation; D010902:Pituitary Gland / Q000502:physiology; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic
chemical_list: D037201:Follicle Stimulating Hormone, beta Subunit
keywords: cattle; follicle-stimulating hormone beta-subunit; gene expression; naturally occurring mutations; transcription factor binding site