Control of Transcription by Steroid Hormones (original) (raw)
Related papers
Regulation of Transcription by Steroid Hormones
Annals of the New York Academy of Sciences, 1994
Steroid hormones bind to their corresponding receptors in the cytoplasm of responsive cells, and this complex is translocated to the nucleus where the hormonereceptor complex binds to specific DNA sequences located in the regulatory regions of the target gene. These specific DNA sequences are referred to as hormoneresponsive elements (HRE) and act as enhancer elements, such that when the receptor complex binds, transcription is induced. In the absence of ligand, the hormone receptor is maintained in an inactive form by association with other cellular proteins.
Transcriptional regulation by steroid hormones
Steroids, 1996
Steroid hormones influence the transcription of a large number of genes by virtue of their interaction with intracellular receptors, which are modular proteins composed of a ligand binding domain, a DNA binding domain, and several transactivation functions distributed along the molecule. The DNA binding domain is organized around two zinc ions and allows the receptors to bind as homodimers to palindromic DNA sequences, the hormone responsive elements (HRE), in such a way that each homodimer contacts one half of the palindrome. Since the two halves are separated by three base pairs, the two homodimers contact the same face of the double helix. Before hormone binding, the receptors are part of a complex with multiple chaperones which maintain the receptor in its steroid binding conformation. Following hormone binding, the complex dissociates and the receptors bind to HREs in chromatin.
Transcriptional control by steroid hormones
The Journal of Steroid Biochemistry and Molecular Biology, 1992
Smmnary--Gene regulation by steroid hormones leads to induction or repression of particular sets of genes. These effects are mediated by intracellular hormone receptors that, in the unliganded state, are maintained in an inactive form by unknown mechanisms possibly involving association with other cellular proteins. Induction of the mouse mammary tumor virus (MMTV) requires binding of the hormone receptor to a complex hormone-responsive element (HRE) located between 75 and 190 bp upstream from the start of transcription. The interaction of several receptor molecules with the four receptor binding sites in the HRE is highly cooperative on circular DNA molecules and each individual site is needed for optimal induction. In chromatin the HRE is precisely organized in phased nucleosomes. Following hormone treatment and receptor binding, changes in chromatin structure are detected that correlate with binding of transcription factors, including nuclear factor I, to the MMTV promoter. However, though nuclear factor I acts as a basal transcription factor on the MMTV promoter it does not cooperate with the hormone receptors in terms of binding to free DNA, and mutation of the nuclear factor I binding site does not eliminate hormonal stimulation. This residual induction is mediated by octamer motifs, upstream of the TATA box, that bind the ubiquitous transcription factor OTF-1. Mutation of these octamer motifs does not influence basal transcription in vitro, but completely abolishes the stimulatory effect of progesterone receptor.
Nucleic Acids Research, 1989
Normalized dose response-curves for transcriptional activation of reporter genes were obtained by co-transfecting them with increasing amounts of wild-type (wt) progesterone (PR), glucocorticoid (GR) and oestrogen (ER) expression vectors. Marked differences in both shape and magnitude of the stimulation were observed depending on whether HeLa or CV1 cells were transfected. In HeLa cells the transcriptional stimulation from a reporter gene containing the hormone responsive element (RE) present in the mouse mammary tumour virus (MMTV) long terminal repeat (LTR) increased as increasing amounts (from 0.05 to 7.5 pg) of PR expression vector were transfected, whereas no such increase was observed in CV1 cells above 1 pg of the same vector. In contrast, a PR mutant lacking the hormone binding domain (HBD, region E), exhibited increasing constitutive activity with increasing amounts of PR expression vector, such that in CV1 cells, but not in HeLa cells, similar activities were measured for the mutant and wt PR when 5 pg expression vectors were transfected. Western blot analyses indicated that the differences between the two cell lines were not due to differences in the amount of receptor proteins. Using the same MMTV LTR-based reporter gene, cell-specific differences were also detected between the dose-response curves obtained for the human GR and a mutant which lacks the HBD. A PR mutant in which the N-terminal A/B region was deleted exhibited no (CV1 cells) or less than 5% (HeLa cells) of the wt-activity, whereas the corresponding GR mutant stimulated efficiently transcription in both cell lines. Identical studies with the wt human ER or a mutant truncated for the N-terminal A/B region resulted in bell-shaped dose-response curves in both HeLa and CV1 cells, whereas an ER mutant lacking the HBD was weakly active in either cell line.
Superfamily of steroid nuclear receptors: positive and negative regulators of gene expression
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 1991
The nuclear hormone receptor superfamily is characterized by an impressive functional diversity of its members despite a remarkable overall structural unity. A variety of ligands bind specifically to them and these receptors control gene networks that have profound effects on growth, development, and homeostasis. The ligand-receptor complexes recognize transcriptional enhancer DNA sequences, the hormone response elements, resulting in induction or repression of gene activity. The similarity between all these hormone response enhancer elements, as well as between the receptors themselves, indicates a conserved general strategy for the hormonal control of transcription by steroids. The activated receptors bind to responsive promoters and most likely mediate the assembly of stage- and tissue-specific transcription factor complexes that stimulate or inhibit gene expression.
Steroid Hormone Receptors and Signal Transduction Processes
2018
Steroid hormones, i.e., androgens, estrogens, glucocorticoids, mineralocorticoids, and progestins, bind with high affinity to their respective steroid hormone receptors (SR). SRs are members of a family of nuclear receptors (NR). Ligandactivated SRs dissociate from hsp90 chaperone complexes in the cytoplasm and enter the nucleus where they bind to specific DNA sequences: hormone response elements (HREs). SRs interact with coregulator proteins (coactivators and corepressors) as well as chromatin remodeling complexes to regulate target gene expression. In addition, some SRs are also associated with the plasma membrane (PM) and PM proteins. Hormone binding to PM-associated SRs activates G-protein coupled receptors (GPCR) and intracellular signaling pathways ultimately regulating gene transcription and other downstream sequelae. This chapter will review of SR/NR including protein structure, ligand activation, gene regulation, examples of rapid "non-genomic" signaling, and the roles of these receptors in human health and disease.
The Journal of Steroid Biochemistry and Molecular Biology, 1999
Nuclear receptors are ligand-inducible transcription factors which mediate the physiological eects of steroid, thyroid and retinoid hormones. By regulating the assembly of a transcriptional preinitiation complex at the promoter of target genes, they enhance the expression of these genes in response to hormone. Recent evidence suggests that nuclear receptors act in part by recruiting multiple coregulator proteins which may have speci®c functions during transcriptional initiation. Liganded receptors recruit members of the SRC family, a group of structurally and functionally related transcriptional coactivators. Receptors also interact with the transcriptional cointegrators p300 and CBP, which are proposed to integrate diverse aerent signals at hormone-regulated promoters. p300/CBP and members of the SRC coactivator family have intrinsic histone acetyltransferase activity which is believed to disrupt the nucleosomal structure at these promoters. Other nuclear receptor coactivators include a member of the SWI/SNF complex, BRG-1, which couples ATP hydrolysis to chromatin remodelling, and the E3 ubiquitinprotein ligases E6-AP and RPF-1. Finally, nuclear receptor coactivators appear to be organized into preformed subcomplexes, an arrangement that may facilitate their ecient assembly into diverse higher order con®gurations. # Journal of Steroid Biochemistry and Molecular Biology 69 (1999) 3±12 0960-0760/99 $ -see front matter # 1999 Elsevier Science Ltd. All rights reserved. PII: S 0 9 6 0 -0 7 6 0 ( 9 8 ) 0 0 1 4 4 -7
Steroids, 2009
Steroid hormone receptors are members of a family of ligand inducible transcription factors, and regulate the transcriptional activation of target genes by recruiting coregulatory proteins to the preinitiation machinery. The binding of these coregulatory proteins to the steroid hormone receptors is often mediated through their two activation functional domains, AF1, which resides in the Nterminal domain, and the ligand-dependent AF2, which is localized in the C-terminal ligand binding domain. Compared to other important functional domains of the steroid hormone receptors, our understanding of the mechanisms of action of the AF1 are incomplete, in part, due to the fact that, in solution, AF1 is intrinsically disordered (ID). However, recent studies have shown that AF1 must adopt a functionally active and folded conformation for its optimal activity under physiological conditions. In this review, we summarize and discuss current knowledge regarding the molecular mechanisms of AF1-mediated gene activation, focusing on AF1 conformation and coactivator binding. We further propose models for the binding/folding of the AF1 domains of the steroid hormone receptors and their protein-protein interactions. The population of ID AF1 can be visualized as a collection of many different conformations, some of which may be assuming the proper functional folding for other critical target binding partners that result in ultimate assembly of AF1:coactivator complexes and subsequent gene regulation. Knowledge of the mechanisms involved therein will significantly help in understanding how signals from a steroid to a specific target gene are conveyed.