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The mouse Muc5b mucin gene is transcriptionally regulated by thyroid transcription factor-1 (TTF-1) and GATA-6 transcription factors.: Regulation of Muc5b mucin gene by TTF-1 and GATA factors
- Source :
- FEBS Journal, FEBS Journal, 2011, 278 (2), pp.282-94. ⟨10.1111/j.1742-4658.2010.07945.x⟩
- Publication Year :
- 2011
- Publisher :
- HAL CCSD, 2011.
-
Abstract
- International audience; MUC5B is one of the major mucin genes expressed in the respiratory tract. Previous studies in our laboratory have demonstrated that MUC5B is expressed in human lung adenocarcinomas and during lung morphogenesis. Moreover, in human lung adenocarcinoma tissues, a converse correlation between MUC5B and thyroid transcription factor-1 (TTF-1) expression, a lung-specific transcription factor, has been established. However, the molecular mechanisms that govern the regulation of MUC5B expression in the lung are largely unknown. In order to better understand the biological role of MUC5B in lung pathophysiology, we report the characterization of the promoter region of the mouse Muc5b mucin gene. The promoter is flanked by a TATA box (TACATAA) identical to that in the human gene. Human and murine promoters share 67.5% similarity over the first 170 nucleotides. By RT-PCR, co-transfection studies and gel-shift assays, we show that Muc5b promoter activity is completely inhibited by TTF-1, whereas factors of the GATA family (GATA-4/GATA-5/GATA-6) are activators. Together, these results demonstrate, for the first time, that Muc5b is a target gene of transcription factors (TTF-1, GATA-6) involved in lung differentiation programs during development and carcinogenesis, and identify TTF-1 as a strong repressor of Muc5b. The characterization of the structural and functional features of the Muc5b mucin gene will provide us with a strong base to develop studies in murine models aimed at the identification of its biological role in lung pathophysiology.
- Subjects :
- MESH: Cell Nucleus
MESH: Gene Expression
MESH: Cell Line, Tumor
MESH: GATA6 Transcription Factor
[SDV.CAN]Life Sciences [q-bio]/Cancer
MESH: Base Sequence
MESH: Adenocarcinoma, Bronchiolo-Alveolar
TTF1
MESH: Sequence Homology, Nucleic Acid
MESH: GATA4 Transcription Factor
lung
mucin
[SDV.CAN] Life Sciences [q-bio]/Cancer
MESH: Promoter Regions, Genetic
MESH: Protein Binding
MESH: Animals
MESH: Mice
Muc5b
MESH: Humans
MESH: Molecular Sequence Data
GATA
MESH: Mucin-5B
MESH: Transfection
MESH: Adenocarcinoma
MESH: DNA
differentiation
MESH: Transcription Factors
respiratory system
MESH: Sequence Deletion
MESH: GATA5 Transcription Factor
MESH: Gene Expression Regulation
MESH: Lung Neoplasms
MESH: Adenocarcinoma, Papillary
MESH: Nuclear Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 1742464X and 17424658
- Database :
- OpenAIRE
- Journal :
- FEBS Journal, FEBS Journal, 2011, 278 (2), pp.282-94. ⟨10.1111/j.1742-4658.2010.07945.x⟩
- Accession number :
- edsair.od......1398..ae4eface1ab1a91d320b85f53c0aa0d1