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Characterization of response elements for androgens, glucocorticoids and progestins in mouse mammary tumour virus
1Molecular Endocrinology Laboratory, Imperial Cancer Research Fund, London, UK.
Abstract:
We have characterized steroid response elements in mouse mammary tumour virus (MMTV) by transient transfection. Four partial inverted repeats of the sequence TGTTCT function as response elements for androgen, as well as for glucocorticoid and progestins, although the relative hormone inductions mediated by each oligonucleotide were different. Mutational analysis of the left half of the palindrome showed that a perfect dyad symmetry is not required for optimum activity as a steroid response element. To investigate potential interactions between steroid receptors and transcription factors we have analysed the minimum sequence requirements for a hormone response. Interestingly, a single 15 bp steroid response element and a TATA box are sufficient for steroid inductions. When the distance between the two elements was increased by up to two turns of the helix the hormone induction initially increased and then gradually declined with no obvious periodicity.
Insights
Researchers identified specific DNA sequences in mouse mammary tumour virus (MMTV) that respond to androgens, glucocorticoids, and progestins. These steroid response elements are crucial for hormone-induced gene expression, even without perfect symmetry.
Area of Science:
- Molecular biology
- Genetics
- Endocrinology
Background:
- Steroid hormones regulate gene expression by binding to specific DNA sequences called steroid response elements (SREs).
- The mouse mammary tumour virus (MMTV) is a well-studied model for understanding hormone-regulated gene expression.
Purpose of the Study:
- To characterize the steroid response elements within the mouse mammary tumour virus (MMTV).
- To investigate the sequence requirements for optimal activity of SREs and their interaction with transcription factors.
Main Methods:
- Transient transfection assays were used to analyze the function of identified DNA sequences.
- Mutational analysis was performed to determine the critical regions within the SREs for hormone response.
Main Results:
- Four partial inverted repeats of the TGTTCT sequence were identified as functional SREs for androgens, glucocorticoids, and progestins.
- Optimal SRE activity does not necessitate perfect dyad symmetry, as indicated by mutational analysis.
- A single 15 bp SRE and a TATA box are sufficient for steroid-induced gene expression.
- Varying the distance between the SRE and TATA box influenced hormone induction levels.
Conclusions:
- The characterized TGTTCT repeats are key regulatory elements mediating steroid hormone action in MMTV.
- Understanding SRE structure-function relationships provides insights into hormone-receptor interactions and transcriptional regulation.