title: Transcriptional regulation of the human KiSS1 gene.
abstract: Kisspeptin, the product of the KiSS1 gene, has emerged as a key component of the mechanism by which the hypothalamus controls puberty and reproductive development. It does so by stimulating the secretion of gonadotropin releasing hormone (GnRH). Little is known about the transcriptional control of the KiSS1 gene. Here we show that a set of proteins postulated to be upstream components of a hypothalamic network involved in controlling female puberty regulates KiSS1 transcriptional activity. Using RACE-PCR we determined that transcription of KiSS1 mRNA is initiated at a single transcription start site (TSS) located 153-156bp upstream of the ATG translation initiation codon. Promoter assays performed using 293 MSR cells showed that the KiSS1 promoter is activated by TTF1 and CUX1-p200, and repressed by EAP1, YY1, and CUX1-p110. EAP1 and CUX-110 were also repressive in GT1-7 cells. All four TFs are recruited in vivo to the KiSS1 promoter and are expressed in kisspeptin neurons. These results suggest that expression of the KiSS1 gene is regulated by trans-activators and repressors involved in the system-wide control of mammalian puberty.
authors.affiliation: Institute of Clinical Biochemistry, Hannover Medical School, Germany.
authors.forename: Johanna K
authors.initials: JK
authors.lastname: Mueller
authors.forename: Anja
authors.initials: A
authors.lastname: Dietzel
authors.forename: Alejandro
authors.initials: A
authors.lastname: Lomniczi
authors.forename: Alberto
authors.initials: A
authors.lastname: Loche
authors.forename: Katrin
authors.initials: K
authors.lastname: Tefs
authors.forename: Wieland
authors.initials: W
authors.lastname: Kiess
authors.forename: Thomas
authors.initials: T
authors.lastname: Danne
authors.forename: Sergio R
authors.initials: SR
authors.lastname: Ojeda
authors.forename: Sabine
authors.initials: S
authors.lastname: Heger
mesh_terms: D047369:Chromatin Immunoprecipitation; D005260:Female; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D059648:Kisspeptins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011627:Puberty / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
chemical_list: C106628:KISS1 protein, human; D059648:Kisspeptins; D012333:RNA, Messenger; D015534:Trans-Activators