ArticleMolecular and cellular biology2016
A Positive Feedback Loop between Glial Cells Missing 1 and Human Chorionic Gonadotropin (hCG) Regulates Placental hCGβ Expression and Cell Differentiation.
Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Directed differentiation of bovine trophoblast stem cells: A useful in vitro model for placenta development.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Trophoblast differentiation in the bovine placenta.The Journal of reproduction and development · 2026Review
- Gcm1 Orchestrates Lef1 Expression in Folate Deficiency-Induced Neural Tube Defects.Molecular neurobiology · 2025Article
- Downregulation of SPARC Expression Enhances the Fusion of BeWo Choriocarcinoma Cells.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- Regulators involved in trophoblast syncytialization in the placenta of intrauterine growth restriction.Frontiers in endocrinology · 2023Review
- Exploring maternal-fetal interface with in vitro placental and trophoblastic models.Frontiers in cell and developmental biology · 2023Review
- Early human trophoblast development: from morphology to function.Cellular and molecular life sciences : CMLS · 2022Review
- Functional antagonism between ΔNp63α and GCM1 regulates human trophoblast stemness and differentiation.Nature communications · 2022Article
- Article
- HtrA4 is up-regulated during trophoblast syncytialization and BeWo cells fail to syncytialize without HtrA4.Scientific reports · 2021Article
- Tracking placental development in health and disease.Nature reviews. Endocrinology · 2020Review
- New insights into the regulation of placental growth factor gene expression by the transcription factors GCM1 and DLX3 in human placenta.The Journal of biological chemistry · 2018Article
- Glial Cells Missing 1 Regulates Equine Chorionic Gonadotrophin Beta SubunitFrontiers in endocrinology · 2018Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human chorionic gonadotropin (hCG) is composed of a common α subunit and a placenta-specific β subunit. Importantly, hCG is highly expressed in the differentiated and multinucleated syncytiotrophoblast, which is formed via trophoblast cell fusion and stimulated by cyclic AMP (cAMP). Although the ubiquitous activating protein 2 (AP2) transcription factors TFAP2A and TFAP2C may regulate hCGβ expression, it remains unclear how cAMP stimulates placenta-specific hCGβ gene expression and trophoblastic differentiation. Here we demonstrated that the placental transcription factor glial cells missing 1 (GCM1) binds to a highly conserved promoter region in all six hCGβ paralogues by chromatin immunoprecipitation-on-chip (ChIP-chip) analyses. We further showed that cAMP stimulates GCM1 and the CBP coactivator to activate the hCGβ promoter through a GCM1-binding site (GBS1), which also constitutes a previously identified AP2 site. Given that TFAP2C may compete with GCM1 for GBS1, cAMP enhances the association between the hCGβ promoter and GCM1 but not TFAP2C. Indeed, the hCG-cAMP-protein kinase A (PKA) signaling pathway also stimulates Ser269 and Ser275 phosphorylation of GCM1, which recruits CBP to mediate GCM1 acetylation and stabilization. Consequently, hCG stimulates the expression of GCM1 target genes, including the fusogenic protein syncytin-1, to promote placental cell fusion. Our study reveals a positive feedback loop between GCM1 and hCG regulating placental hCGβ expression and cell differentiation.
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