Ligand-, Cell-, and Estrogen Receptor Subtype (α/β)-dependent Activation at GC-rich (Sp1) Promoter Elements*
By B. Saville, M. Wormke, Fan Wang, T. Nguyen, E. Enmark, G. Kuiper, Jan-Ake Gustafsson, S. Safe. Journal of Biological Chemistry, 2000
370 citations recorded by the source corpus.
17β-Estradiol (E2) induces expression of several genes via estrogen receptor (ER)-Sp1 protein interactions with GC-rich promoter elements in which Sp1 but not ER binds DNA. This study reports the ligand- and cell context-dependent ERα/Sp1 and ERβ/Sp1 action using an E2-responsive construct (pSp1) containing a GC-rich promoter. Both ERα and ERβ proteins physically interact with Sp1 (coimmunoprecipitation) and preferentially bind to the C-terminal region of this protein in pull-down assays. E2- and antiestrogen-dependent transcriptional activation of ERα/Sp1 was observed in MCF-7, MDA-MB-231, and LnCaP cells, but not in HeLa cells. E2 did not affect or significantly decrease ERβ/Sp1 action, and antiestrogens had minimal effects in the same 4 cell lines. Exchange of activation function-1 (AF-1) domains of ER subtypes gave chimeric ERα/β(AF-1α/AF-2β) and ERβ/α (AF-1β/AF-2α) proteins that resembled wild-type ER (α or β) in terms of physical association with Sp1 protein. Transcriptional activation studies with chimeric ERβ/α and ERα/β showed that only ERα/β can activate transcription from an Sp1 element, not ERβ/α. This indicates that the AF-1 domain from ERα is responsible for activation at an Sp1 element, independent of ER subtype context. In order to further characterize this observation, deletion constructs in the AF-1 domain of both ERα and ERα/β were made, and transactivation studies indicated that the region between amino acids 79 and 117 of this domain is important for activation at an Sp1 element.
Subfields: Genetics, Molecular Biology, Pharmacology
View Paper: https://www.semanticscholar.org/paper/3d190cc25453020bfec72198151c3f06a4d5eb34
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- J. Simard
Citations in the corpus
- Molecular Biology of the 3-Hydroxysteroid Dehydrogenase/5-4 Isomerase Gene Family (2005, background): “Some studies have suggested that some of the important regulatory elements for this gene are localized in the first intron of the HSD3B1 gene (160) with an element overlapping an Sp1 motif.”