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Placenta-specific INSL4 expression is mediated by a human endogenous retrovirus element
Ivan Bièche1, Anne Laurent, Ingrid Laurendeau
1Laboratoire de Génétique Moléculaire, Faculté des Sciences Pharmaceutiques et Biologiques, Univeristé René Descartes, Paris, France.
Biology of Reproduction
|February 28, 2003
Summary
Ancient retroviral elements integrated into the human INSL4 gene promoter drive its placenta-specific expression, highlighting retroviral impact on primate evolution and placental function.
Area of Science:
- Genomics
- Evolutionary Biology
- Reproductive Biology
Background:
- Human insulin-family genes regulate vital cellular processes.
- INSL4 is unique among these for its placenta-specific expression.
- The INSL4 gene's evolutionary origins and regulatory mechanisms are largely unknown.
Purpose of the Study:
- To investigate the genomic organization and evolutionary history of the human INSL4 gene.
- To elucidate the regulatory elements controlling INSL4's placenta-specific expression.
- To explore the role of endogenous retroviruses in INSL4 gene regulation and primate evolution.
Main Methods:
- Comparative genomics to analyze gene clustering and primate-specificity.
- Identification and characterization of inserted elements within the INSL4 promoter region.
- Transient transfection assays to assess the functional role of HERV elements in gene expression.
- Analysis of INSL4 mRNA splicing variants.
Main Results:
- The human INSL4 gene is clustered with other insulin superfamily members on chromosome 9p23.3-p24.1.
- INSL4 appears to be primate-specific, with its emergence and HERV insertion post-monkey divergence.
- A human endogenous retrovirus (HERV) element within the INSL4 promoter, specifically its 3' LTR, mediates placenta-specific expression and up-regulation.
- An alternatively spliced INSL4 mRNA encoding novel peptides was identified.
Conclusions:
- Ancient retroviral elements have significantly influenced the functional evolution of the human placenta.
- The HERV insertion in the INSL4 promoter is crucial for its placental expression, suggesting retroviral domestication.
- This finding underscores the substantial role of endogenous retroviruses in shaping primate genomes and reproductive biology.
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