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Rapid induction of GATA transcription factors in developing mouse intestine following glucocorticoid administration.
- Source :
-
American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2004 Jun; Vol. 286 (6), pp. G947-53. Date of Electronic Publication: 2004 Jan 22. - Publication Year :
- 2004
-
Abstract
- In the developing intestine, transcription of alpha-glucosidase genes such as sucrase-isomaltase and trehalase is stimulated by glucocorticoid administration. The consequent increase of their respective mRNAs is characterized by a 12-h lag, suggesting that the response to glucocorticoids represents a secondary effect. We hypothesized that the primary response of the tissue to glucocorticoids includes induction of one or more intestinal transcription factors. To investigate this hypothesis, we identified a region in the mouse trehalase promoter (located at nucleotides -406 to -377 from the transcription start site) with potential binding sites for three transcription factors: Cdx-2, GATA, and C/EBP. Gel shifts were performed using labeled oligonucleotides from this region with nuclear extracts from jejunums of either control 8-day-old mouse pups or littermates treated with dexamethasone (DEX) 4 h before death. A specific shifted band was observed with DEX extracts but not with control extracts. Supershift assays indicated the presence of GATA-4 and GATA-6 but not GATA-5 nor Cdx-2, C/EBP alpha, C/EBP beta, or C/EBP delta. GATA binding was further implicated by competition studies with mutated oligonucleotides. Finally, Western blot analysis showed GATA-4 and GATA-6 proteins in DEX but not control nuclear extracts. For GATA-4, the same pattern was demonstrated with whole cell extracts and with the cytosol fraction. We conclude that expression of GATA-4 and GATA-6 proteins in the suckling mouse jejunum is stimulated by DEX. This novel finding constitutes an important first step in understanding the molecular mechanism of glucocorticoid action on the developing intestine.
- Subjects :
- Animals
Base Sequence
Conserved Sequence
DNA Mutational Analysis
GATA4 Transcription Factor
GATA6 Transcription Factor
Jejunum drug effects
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Promoter Regions, Genetic genetics
Sucrase-Isomaltase Complex genetics
Trehalase genetics
Animals, Suckling metabolism
DNA-Binding Proteins biosynthesis
Dexamethasone pharmacology
Glucocorticoids pharmacology
Jejunum metabolism
Transcription Factors biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0193-1857
- Volume :
- 286
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Gastrointestinal and liver physiology
- Publication Type :
- Academic Journal
- Accession number :
- 14739144
- Full Text :
- https://doi.org/10.1152/ajpgi.00470.2003