A 13 bp palindrome is a functional estrogen responsive element and interacts specifically with estrogen receptor
TL;DR: This work has defined the 13 bp palindrome GGTCACAGTGACC as a minimal functional estrogen responsive element (ERE), which binds estrogen receptor preferentially in vitro and point mutations within the ERE decrease its affinity for the estrogen receptor and result in a complete loss of estrogen inducibility.
Abstract: Sequences located upstream of the transcription initiation site of the Xenopus vitellogenin A2 (vit A2) gene contain a hormone dependent enhancer that confers estrogen control to the heterologous thymidine kinase (tk) promoter. As a minimal functional estrogen responsive element (ERE), we have defined the 13 bp palindrome GGTCACAGTGACC. This ERE binds estrogen receptor preferentially in vitro. Although the ERE shares some structural features with the glucocorticoid responsive element (GRE) it is distinct from this element since it neither binds glucocorticoid receptor in vitro nor does it confer glucocorticoid inducibility to a fusion gene. Point mutations within the ERE decrease its affinity for the estrogen receptor and result in a complete loss of estrogen inducibility.
Citations
More filters
TL;DR: In addition to inducing the activation function associated with the HBD, estrogen plays a crucial role in the formation of stable ER dimers that bind tightly to ERE.
1,178 citations
Cites background from "A 13 bp palindrome is a functional ..."
...binding was observed with a GRE or the ERE mutants C and D (Table i), which cannot mediate the ER effect in vivo (Klock et al., 1987; Klein-Hitpap et al., 1988)....
[...]
TL;DR: Review of data from the own laboratory and those in the literature indicate that ERalpha binding affinity does not relate linearly with E(2)-induced transcriptional activation, and it is suggested that the reasons for this discord include cellular amounts of coactivators and adaptor proteins that play roles both in ER binding and transcriptionalactivation; phosphorylation of ER and other proteins involved in transcriptional activated; and sequence-specific and protein-induced alterations in chromatin architecture.
Abstract: The estrogen receptor (ER) is a ligand-activated enhancer protein that is a member of the steroid/nuclear receptor superfamily. Two genes encode mammalian ER: ERα and ERβ. ER binds to specific DNA sequences called estrogen response elements (EREs) with high affinity and transactivates gene expression in response to estradiol (E2). The purpose of this review is to summarize how natural and synthetic variations in the ERE sequence impact the affinity of ER–ERE binding and E2-induced transcriptional activity. Surprisingly, although the consensus ERE sequence was delineated in 1989, there are only seven natural EREs for which both ERα binding affinity and transcriptional activation have been examined. Even less information is available regarding how variations in ERE sequence impact ERβ binding and transcriptional activity. Review of data from our own laboratory and those in the literature indicate that ERα binding affinity does not relate linearly with E2-induced transcriptional activation. We suggest that the reasons for this discord include cellular amounts of coactivators and adaptor proteins that play roles both in ER binding and transcriptional activation; phosphorylation of ER and other proteins involved in transcriptional activation; and sequence-specific and protein-induced alterations in chromatin architecture.
1,010 citations
Cites background from "A 13 bp palindrome is a functional ..."
...This ERE sequence was shown to act on a heterologous promoter in an orientation- and distance-independent manner, thus fitting the definition of an enhancer element, as understood at that time (37)....
[...]
...Klinge, manuscript submitted), indicating that the minimal ERE should be considered to be EREc15 and not EREc13 as earlier reported (37)....
[...]
...The derived minimal consensus ERE sequence is a 13 bp palindromic inverted repeat (IR): 5′-GGTCAnnnTGACC-3′ (37), and differs in only 2 bp in each half-site from the GRE (38)....
[...]
TL;DR: It is hoped that the forthcoming information will generate new ideas and concepts for a process that is essential for maintaining procreation and solving major reproductive health issues in women.
Abstract: Successful implantation is the result of reciprocal interactions between the implantation-competent blastocyst and receptive uterus. Although various cellular aspects and molecular pathways of this dialogue have been identified, a comprehensive understanding of the implantation process is still missing. The receptive state of the uterus, which lasts for a limited period, is defined as the time when the uterine environment is conducive to blastocyst acceptance and implantation. A better understanding of the molecular signals that regulate uterine receptivity and implantation competency of the blastocyst is of clinical relevance because unraveling the nature of these signals may lead to strategies to correct implantation failure and improve pregnancy rates. Gene expression studies and genetically engineered mouse models have provided valuable clues to the implantation process with respect to specific growth factors, cytokines, lipid mediators, adhesion molecules, and transcription factors. However, a staggering amount of information from microarray experiments is also being generated at a rapid pace. If properly annotated and explored, this information will expand our knowledge regarding yet-to-be-identified unique, complementary, and/or redundant molecular pathways in implantation. It is hoped that the forthcoming information will generate new ideas and concepts for a process that is essential for maintaining procreation and solving major reproductive health issues in women.
994 citations
Cites background from "A 13 bp palindrome is a functional ..."
...Although a perfect palindromic consensus was identified as AGGTCA(nnn)TGACCT (66), most estrogen-responsive genes have imperfect palindromes or do not have recognizable EREs (65, 67–70)....
[...]
TL;DR: Receptors for retinoic acid, vitamin D3 and the steroid and thyroid hormones belong to a family of ligand-activated enhancer-binding factors which are composed of a number of functional domains required for ligand and DNA binding, nuclear translocation, dimerization and trans -activation of transcription.
987 citations
TL;DR: A novel RAR subtype is discovered whose expression in adult mouse seems to be highly restricted to skin, whereas RARα and RARβ are expressed in a variety of adult tissues, which suggests strongly that RAR α- and β-subtypes have different functions.
Abstract: In addition to having profound effects on embryonic pattern formation, retinoic acid (RA) has striking effects on differentiation and maintenance of epithelial cells in vivo and in vitro Skin is a major target organ for retinoids both in its normal and pathological states. The discovery of two human nuclear receptors for RA (hRAR alpha and hRAR beta) acting as transcriptional RA-inducible enhancer factors has provided a basis for understanding how RA controls gene expression. To investigate the specific role that RARs might play during development and in adult tissues, we have cloned the mouse RAR alpha and RAR beta (mRAR alpha and mRAR beta). Their amino-acid sequences are much more homologous to those of hRAR alpha and hRAR beta, respectively, than to each other, which suggests strongly that RAR alpha- and beta-subtypes have different functions. Most interestingly we have discovered a novel RAR subtype (mRAR gamma) whose expression in adult mouse seems to be highly restricted to skin, whereas RAR alpha and RAR beta are expressed in a variety of adult tissues. Furthermore, both mRAR alpha and mRAR gamma RNAs are readily detected in undifferentiated F9 embryocarcinoma (EC) cells, whereas mRAR beta messenger RNA is induced at least 30-fold in RA-differentiated F9 cells.
747 citations
References
More filters
Book•
22 Jul 1983
TL;DR: The authors discuss the latest advances in molecular endocrinology: - steroid receptor binding to DNA sequences of hormonally controlled genes, - structure of genes controlled by steroid hormones, - heterogeneity of steroid receptors, - immunochemical approaches to receptor studies, and - the most recent approaches to steroid hormone action and biological response.
Abstract: In this book, the authors discuss the latest advances in molecular endocrinology: - steroid receptor binding to DNA sequences of hormonally controlled genes, - structure of genes controlled by steroid hormones, - heterogeneity of steroid receptors, - immunochemical approaches to receptor studies, and - the most recent approaches to steroid hormone action and biological response. The Contents discussed are: Biochemical Evidence for the Exclusive Nuclear Localization of the Estrogen Receptor. - Structure, Dynamics, and Cloning of the Estrogen Receptor. - Structure, Dynamics, and Cloning of the Estrogen Receptor - Physical and Functional Parameters of Isolated Estrogen Receptor - Type II Binding Sites: Cellular Origin and an Endogeneous Ligand. - The Two Phosphorylation Reactions of the Progesterone Receptor. - Receptor Mediated Action of the Vitamin D Hormone. - Characterization of the Nuclear Binding Sites (Acceptor Sites) for a Steroid Receptor. Antibodies in Estrogen, Progesterone, Glucocorticoid, Vitamin D Receptors and Autoantibodies to Antrogene Receptor. - Isolation and Characterization of cDNA probes for Human CBG and Rat ABP. Ornithine Decarboxy lase mRNAs in Murine Kidney: Structure and Regulation by Androgens - Glucocorticoid Receptors and the Control of Gene Expression. - Activation and Regulation of the Vitellogenin Gene Family. - Intra- and Intercellular Aspectsmore » of the Hormonal Regulation of the ..cap alpha..2..mu.. Globulin Gene Expression. - Hormonal Regulation of Sexually Differentiated Isozymes of Cytochrome P-450 in Rat Liver. - Interaction of Thyroid Hormone and Carbohydrates on Hepatic Gene Expression.« less
79 citations
Book•
01 Jan 1983
TL;DR: Do you know the authors' friends become fans of molecular biology of egg maturation as the best book to read?
Abstract: molecular biology of egg maturation What to say and what to do when mostly your friends love reading? Are you the one that don't have such hobby? So, it's important for you to start having that hobby. You know, reading is not the force. We're sure that reading will lead you to join in better concept of life. Reading will be a positive activity to do every time. And do you know our friends become fans of molecular biology of egg maturation as the best book to read? Yeah, it's neither an obligation nor order. It is the referred book that will not make you feel disappointed.
36 citations