ArticleMolecular endocrinology (Baltimore, Md.)2010
Enhancers of GnRH transcription embedded in an upstream gene use homeodomain proteins to specify hypothalamic expression.
Article in Molecular endocrinology (Baltimore, Md.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Haploinsufficiency of Sox2 causes fewer GnRH neurons and delayed puberty in mice.Endocrinology · 2026Article
- In vitro modeling of cranial placode differentiation: Recent advances, challenges, and perspectives.Developmental biology · 2024Review
- Article
- Lactate-Dependent Cross-Talk Between Astrocyte and GnRH-I Neurons in Hypothalamus of Aged Brain: Decreased GnRH-I Transcription.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
- FSHB Transcription is Regulated by a Novel 5' Distal Enhancer With a Fertility-Associated Single Nucleotide Polymorphism.Endocrinology · 2021Article
- Differential CRE Expression in Lhrh-cre and GnRH-cre Alleles and the Impact on Fertility in Otx2-Flox Mice.Neuroendocrinology · 2019Article
- Nasal Placode Development, GnRH Neuronal Migration and Kallmann Syndrome.Frontiers in cell and developmental biology · 2019Article
- Transcriptional interaction between cFOS and the homeodomain-binding transcription factor VAX1 on the GnRH promoter controls Gnrh1 expression levels in a GnRH neuron maturation specific manner.Molecular and cellular endocrinology · 2018Article
- Chromatin status and transcription factor binding to gonadotropin promoters in gonadotrope cell lines.Reproductive biology and endocrinology : RB&E · 2017Article
- Development of Gonadotropin-Releasing Hormone-Secreting Neurons from Human Pluripotent Stem Cells.Stem cell reports · 2016Article
- Mice carrying a human GLUD2 gene recapitulate aspects of human transcriptome and metabolome development.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Deletion of Vax1 from Gonadotropin-Releasing Hormone (GnRH) Neurons Abolishes GnRH Expression and Leads to Hypogonadism and Infertility.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Article
- Maternal dexamethasone exposure during pregnancy in rats disrupts gonadotropin-releasing hormone neuronal development in the offspring.Cell and tissue research · 2014Article
- Neurokinin B causes acute GnRH secretion and repression of GnRH transcription in GT1-7 GnRH neurons.Molecular endocrinology (Baltimore, Md.) · 2013Article
- Androgen receptor repression of gonadotropin-releasing hormone gene transcription via enhancer 1.Molecular and cellular endocrinology · 2012Article
- Cell-type specific expression of oxytocin and vasopressin genes: an experimental odyssey.Journal of neuroendocrinology · 2012Review
- Androgen receptor repression of GnRH gene transcription.Molecular endocrinology (Baltimore, Md.) · 2012Article
- Mutational analysis of the necdin gene in patients with congenital isolated hypogonadotropic hypogonadism.European journal of endocrinology · 2011Article
- Dynamic chromatin modifications control GnRH gene expression during neuronal differentiation and protein kinase C signal transduction.Molecular endocrinology (Baltimore, Md.) · 2011Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
GnRH, the central regulator of reproductive function, is produced by only approximately 800 highly specialized hypothalamic neurons. Previous studies identified a minimal promoter [GnRH minimal promoter (GnRH-P)] (-173/+1) and a neuron-specific enhancer [GnRH-enhancer (E)1] (-1863/-1571) as regulatory regions in the rat gene that confer this stringent specificity of GnRH expression to differentiated GnRH neurons. In transgenic mice, these two elements target only GnRH neurons but fail to drive expression in the entire population, suggesting the existence of additional regulatory regions. Here, we define two novel, highly conserved, upstream enhancers in the GnRH gene termed GnRH-E2 (-3135/-2631) and GnRH-E3 (-4199/-3895) that increase neuron-specific GnRH expression through interactions with GnRH-E1 and GnRH-P. GnRH-E2 and GnRH-E3 regulate GnRH expression through similar mechanisms via Oct-1, Msx1, and Dlx2, which bind both GnRH-E2 and the GnRH-E3 critical region at -3952/-3895. Overexpression of Dlx2 increases transcription through GnRH-E2 and GnRH-E3. Remarkably, these novel elements are contained within the 3' untranslated region of the neighboring upstream gene, yet are marked endogenously by histone modification signatures consistent with those of enhancers. Thus, GnRH-E2 and GnRH-E3 are novel regulatory elements that, together with GnRH-E1 and GnRH-P, confer the specificity of GnRH expression to differentiated and mature GnRH neurons.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.