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Function of a transcription factor CDX2 beyond its trophectoderm lineage specification
Toshihiro Sakurai1, Hanako Bai, Toshihiro Konno
1Laboratory of Animal Breeding, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
The transcription factor caudal-related homeobox 2 (CDX2) regulates interferon τ (IFNT) gene expression through histone modifications. CDX2 recruits cAMP response element binding protein-binding protein, increasing histone acetylation for IFNT gene regulation.
Area of Science:
- Reproductive Biology
- Epigenetics
- Molecular Biology
Background:
- The transcription factor caudal-related homeobox 2 (CDX2) is known to regulate trophectoderm differentiation.
- Its precise role in regulating specific genes like interferon τ (IFNT) and the underlying mechanisms remain unclear.
Purpose of the Study:
- To investigate the novel role of CDX2 in histone modifications of the interferon τ (IFNT) gene.
- To elucidate the regulatory mechanism by which CDX2 influences IFNT gene expression.
Main Methods:
- Chromatin immunoprecipitation assays in ovine conceptuses at different pregnancy stages.
- Luciferase assays and transfection of CDX2 constructs in bovine fibroblast cells.
- Small interfering RNA (siRNA) treatment to assess CDX2 knockdown effects.
Main Results:
- CDX2 expression and H3K18 acetylation at the IFNT gene peaked on days 14 and 16 of ovine pregnancy, declining thereafter.
- Candidate CDX2 binding sites were identified in the bovine IFNT gene promoter.
- CDX2 transfection increased histone acetylation and recruited cAMP response element binding protein-binding protein (CBP), a histone acetyltransferase.
Conclusions:
- CDX2 plays a significant role in regulating IFNT gene expression via epigenetic modifications.
- CDX2 recruits CBP, leading to increased histone acetylation at the IFNT gene locus.
- This mechanism highlights a new pathway for CDX2-mediated gene regulation in reproductive processes.
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