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Identification of the novel player deltaEF1 in estrogen transcriptional cascades
1Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.
Abstract:
Although many genes are regulated by estrogen, very few have been shown to directly bind the estrogen receptor complex. Therefore, transcriptional cascades probably occur in which the estrogen receptor directly binds to a target gene that encodes another transcription factor that subsequently regulates additional genes. Through the use of a differential display assay, a transcription factor has been identified that may be involved in estrogen transcriptional cascades. This report demonstrates that transcription factor deltaEF1 is induced eightfold by estrogen in the chick oviduct. Furthermore, the regulation by estrogen occurs at the transcriptional level and is likely to be a direct effect of the estrogen receptor complex, as it does not require concomitant protein synthesis. A putative binding site was identified in the 5'-flanking region of the chick ovalbumin gene identifying it as a possible target gene for regulation by deltaEF1. Characterization of this binding site revealed that deltaEF1 binds to and regulates the chick ovalbumin gene. Thus, a novel regulatory cascade that is triggered by estrogen has been defined.
Insights
Estrogen directly regulates transcription factor deltaEF1 in the chick oviduct. This factor then directly binds and regulates the ovalbumin gene, defining a novel estrogen-driven gene cascade.
Area of Science:
- Molecular Endocrinology
- Gene Regulation
- Transcriptional Cascades
Background:
- Estrogen regulates numerous genes, but direct binding of the estrogen receptor complex is rare.
- Transcriptional cascades, involving intermediate transcription factors, are likely key to estrogen's broad gene regulation.
- Identifying these intermediate factors is crucial for understanding estrogenic signaling pathways.
Purpose of the Study:
- To identify transcription factors involved in estrogen-mediated transcriptional cascades.
- To investigate the direct regulation of transcription factor deltaEF1 by estrogen.
- To determine if deltaEF1 directly regulates downstream target genes, such as the ovalbumin gene.
Main Methods:
- Differential display assay to identify novel transcription factors.
- Quantitative analysis of deltaEF1 gene induction by estrogen.
- Analysis of protein synthesis requirement for estrogenic regulation.
- Identification and characterization of deltaEF1 binding sites in the 5'-flanking region of the ovalbumin gene.
Main Results:
- Transcription factor deltaEF1 was identified as potentially involved in estrogenic cascades.
- Estrogen significantly induced deltaEF1 expression eightfold in the chick oviduct at the transcriptional level.
- Estrogenic regulation of deltaEF1 occurred directly, independent of new protein synthesis.
- A specific binding site for deltaEF1 was found in the ovalbumin gene's regulatory region, confirming deltaEF1's role in its regulation.
Conclusions:
- A novel estrogen-induced transcriptional cascade has been elucidated.
- DeltaEF1 acts as a direct mediator of estrogenic signaling.
- The ovalbumin gene is a direct transcriptional target of deltaEF1 in this cascade.