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Mouse Trefoil factor genes: genomic organization, sequences and methylation analyses
S Ribieras1, O Lefèbvre, C Tomasetto
1Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM U184/ULP, BP 163, 67404 Illkirch Cedex, C.U. de, Strasbourg, France.
Gene
|April 6, 2001
Summary
The clustered mammalian Trefoil Factors (TFFs) genes (TFF1, TFF2, TFF3) are regulated by epigenetic mechanisms. Promoter methylation patterns correlate with TFF gene expression in the gastrointestinal tract.
Area of Science:
- Genetics
- Epigenetics
- Gastroenterology
Background:
- Mammalian Trefoil Factors (TFFs), including TFF1, TFF2, and TFF3, are secreted proteins crucial for gastrointestinal epithelial barrier protection and repair.
- These TFFs are expressed in a specific, complementary pattern throughout the gastrointestinal tract.
Purpose of the Study:
- To investigate the genomic organization of mouse TFF genes.
- To analyze the epigenetic regulation of TFF gene expression, focusing on promoter methylation patterns.
Main Methods:
- Comparative sequence analysis of mouse and human TFF promoter regions.
- Analysis of DNA methylation status in the proximal promoters of TFF1, TFF2, and TFF3 genes in various tissues.
Main Results:
- The three mouse TFF genes (TFF1, TFF2, TFF3) are organized in a cluster within a 40 kb DNA segment in a head-to-tail orientation.
- Conserved regulatory elements were identified in the promoter sequences of mouse and human TFF genes.
- TFF1 and TFF2 promoters are unmethylated, and TFF3 promoter is partially demethylated in tissues expressing these genes.
- Conversely, all three TFF gene promoters are methylated in non-expressing organs.
Conclusions:
- The findings suggest that epigenetic mechanisms, specifically DNA methylation, play a significant role in regulating TFF gene expression.
- These regulatory mechanisms are likely involved in both normal physiological conditions and pathological states within the gastrointestinal tract.