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Loss of Hoxa5 function affects Hox gene expression in different biological contexts
Béatrice Frenette1,2, Josselin Guéno1,2, Nicolas Houde1
1Centre de Recherche sur le Cancer de L'Université Laval, Centre de Recherche du CHU de Québec-Université Laval (Oncology), 1401, 18e Rue, Québec, QC, G1J 1Z4, Canada.
Scientific Reports
|December 28, 2024
Summary
Loss of Hoxa5 gene function impacts gene expression context-specifically. HOXA5 protein primarily regulates Hox gene expression in trans, not through local cis effects.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- The homeobox A5 (Hoxa5) gene is crucial for various developmental processes.
- The precise downstream molecular mechanisms regulated by Hoxa5 remain largely uncharacterized.
Purpose of the Study:
- To investigate the global transcriptional consequences of Hoxa5 gene loss.
- To elucidate the regulatory role of HOXA5, particularly concerning other Hox genes.
Main Methods:
- Bulk RNA sequencing was employed across seven distinct biological contexts.
- Comparative analysis of epigenetic marks in the HoxA cluster was performed in Hoxa5 mutant mouse lines.
Main Results:
- Few common transcriptional changes were observed, indicating context-specific HOXA5 effectors.
- A trend of reduced HoxA gene expression was noted in Hoxa5 null mutants.
- Hoxa5 mutations had minimal impact on the epigenetic landscape of the HoxA cluster.
Conclusions:
- HOXA5 predominantly acts in trans to control gene expression, including other Hox genes.
- The findings argue against significant local cis-regulatory effects contributing to Hoxa5 mutant phenotypes.
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