Erm/thyroid transcription factor 1 interactions modulate surfactant protein C transcription

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• Surfactant protein C (SP-C) expression in lung alveolar type II cells is regulated by thyroid transcription factor 1 (TTF-1).
• The Ets family of transcription factors plays roles in cellular differentiation and gene regulation.

Purpose of the Study:

• To investigate the role of Erm, an Ets family member, in SP-C gene regulation.
• To elucidate the interaction between Erm and TTF-1 in controlling SP-C expression.

Main Methods:

• Analysis of Erm expression in lung epithelium.
• Electrophoretic mobility shift assays and co-transfection assays to study promoter activity.
• Mammalian two-hybrid and co-immunoprecipitation assays to assess protein-protein interactions.
• siRNA-mediated knockdown of Erm in primary alveolar type II cells.

Main Results:

• Erm is expressed in alveolar type II cells and its expression is regulated by fibroblast growth factors (FGFs).
• Erm enhances TTF-1-mediated SP-C transcription through interaction with TTF-1.
• Specific Ets binding sites in the SP-C promoter are critical for Erm's regulatory function.
• siRNA targeting Erm reduces both Erm and SP-C expression in alveolar type II cells.

Conclusions:

• Erm is a novel regulator of SP-C expression in lung alveolar type II cells.
• Erm functions in conjunction with TTF-1, involving direct protein-protein interactions.
• FGF signaling influences SP-C regulation via modulation of Erm expression.