Transcriptional regulation of the human KiSS1 gene.
Mueller. Johanna K JK; Dietzel. Anja A; Lomniczi. Alejandro A; Loche. Alberto A; Tefs. Katrin K; Kiess. Wieland W; Danne. Thomas T; Ojeda. Sergio R SR; Heger. Sabine S
Key Findings
- KiSS1 transcription starts at a single start site 153‑156 bp upstream of the ATG codon.
- Activators TTF1 and CUX1‑p200 increase KiSS1 promoter activity.
- Repressors EAP1, YY1, and CUX1‑p110 decrease KiSS1 promoter activity and also act in GT1‑7 cells.
- All four transcription factors bind the KiSS1 promoter in vivo and are present in kisspeptin neurons.
Practical Outcomes
- This research is mainly basic science and doesn’t change current kisspeptin dosing or usage. It highlights potential future targets (the identified transcription factors) for modulating kisspeptin levels, but no actionable protocols are available yet.
Summary
The paper maps how the kisspeptin gene (KiSS1) is turned on and off in brain cells that control puberty, showing which proteins boost its activity and which suppress it, but it doesn’t give any direct tips for using kisspeptin as a supplement or therapy.
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.
Study Information
pubmed
2011
2011-06-06T00:00:00.000Z
10.1016/j.mce.2011.04.025
63
72