Nuclear Receptors: One Big Family

McEwan, Iain J.

doi:10.1007/978-1-60327-575-0_1

Cited by 117 publications

(86 citation statements)

References 50 publications

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“…Signaling pathways initiated by steroid hormones, such as 17␤-estradiol (E2), provide model systems to study these different layers of transcription regulation in mammalian cells. Indeed, exposure to estrogens leads to transcriptional changes to cell-specific gene repertoires, which are mediated by E2-bound estrogen receptors (ESR1 [referred to as ER throughout this report] and ESR2) (6). On model gene promoters, such as TFF1, ER together with a number of its cofactors associates with cognate binding sites (BSs) in a cyclic manner to direct their transcription (7,8).…”

mentioning

confidence: 99%

Dynamic Estrogen Receptor Interactomes Control Estrogen-Responsive Trefoil Factor (TFF) Locus Cell-Specific Activities

Quintin

Péron

Palierne

et al. 2014

Molecular and Cellular Biology

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f Estradiol signaling is ideally suited for analyzing the molecular and functional linkages between the different layers of information directing transcriptional regulations: the DNA sequence, chromatin modifications, and the spatial organization of the genome. Hence, the estrogen receptor (ER) can bind at a distance from its target genes and engages timely and spatially coordinated processes to regulate their expression. In the context of the coordinated regulation of colinear genes, identifying which ER binding sites (ERBSs) regulate a given gene still remains a challenge. Here, we investigated the coordination of such regulatory events at a 2-Mb genomic locus containing the estrogen-sensitive trefoil factor (TFF) cluster of genes in breast cancer cells. We demonstrate that this locus exhibits a hormone-and cohesin-dependent reduction in the plasticity of its three-dimensional organization that allows multiple ERBSs to be dynamically brought to the vicinity of estrogen-sensitive genes. Additionally, by using triplex-forming oligonucleotides, we could precisely document the functional links between ER engagement at given ERBSs and the regulation of particular genes. Hence, our data provide evidence of a formerly suggested cooperation of enhancers toward gene regulation and also show that redundancy between ERBSs can occur.

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mentioning

confidence: 99%

Dynamic Estrogen Receptor Interactomes Control Estrogen-Responsive Trefoil Factor (TFF) Locus Cell-Specific Activities

Quintin

Péron

Palierne

et al. 2014

Molecular and Cellular Biology

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“…All members of the nuclear receptor family share a common protein structure and are made up of a central DNA-binding domain (DBD), a carboxyl-terminal ligand-binding domain (LBD), and varying numbers of activation function (AF) elements ( Figure 1-2A ) ( 42 ). The current understanding of the mechanisms by which these steroid hormones act has largely evolved from cell line studies, and whether these mechanisms accurately refl ect what occurs in the normal human breast in vivo remains to be shown.…”

Section: Mechanisms Of Hormonal Action On Breast Tissuementioning

confidence: 99%

1. Estrogen and Progestin Stimulation of Breast Proliferation

Hilton¹,

Graham²,

Clarke³

2012

Translational Endocrinology &Amp; Metabolism

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The ovarian steroid hormones estrogen and progesterone are critical in the growth and proliferation of the breast during normal development, yet ovarian activity has also been shown to be a major driver of breast cancer risk. Through both the menstrual cycle and pregnancy, healthy women are frequently exposed to changes in their hormonal milieu, during which cycling estrogen and progesterone levels induce the breast to undergo signifi cant morphological changes. This infl uence, and the fact that exposure to exogenous hormones such as the use of progestins in hormone replacement therapy and oral contraception are associated with increased breast cancer risk, highlights the importance of understanding the molecular mechanisms of estrogen and progesterone signaling, both in the normal breast and in the development and progression of breast cancer. Importantly, due to the limited availability of normal human breast tissue, the vast majority of current knowledge of the mechanisms of these hormones has evolved from animal models and cell line studies, and recapitulation of these mechanisms in the normal human breast largely remains to be confi rmed. Here the authors review the current thinking on ovarian hormone action in the human breast and discuss the implications these effects may have on breast cancer risk throughout a woman's lifetime.

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“…The superfamily of nuclear receptors (NRs) present in vertebrates, arthropods and nematodes plays crucial roles in the regulation of transcription, and is involved in various stages of development, maintaining the control of homeostasis and causing or preventing cellular proliferation, differentiation and death (McEwan, 2009). Some 48 members have been found in the human genome, and a smaller group in arthropoda, housing around 21 in Drosophila melanogaster.…”

Section: Transcription Regulation By Nuclear Hormone Receptorsmentioning

confidence: 99%

Structural insights into transcription complexes

Berger

Blanco

Boelens

et al. 2011

Journal of Structural Biology

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a b s t r a c tControl of transcription allows the regulation of cell activity in response to external stimuli and research in the field has greatly benefited from efforts in structural biology. In this review, based on specific examples from the European SPINE2-COMPLEXES initiative, we illustrate the impact of structural proteomics on our understanding of the molecular basis of gene expression. While most atomic structures were obtained by X-ray crystallography, the impact of solution NMR and cryo-electron microscopy is far from being negligible. Here, we summarize some highlights and illustrate the importance of specific technologies on the structural biology of protein-protein or protein/DNA transcription complexes: structure/ function analysis of components the eukaryotic basal and activated transcription machinery with focus on the TFIID and TFIIH multi-subunit complexes as well as transcription regulators such as members of the nuclear hormone receptor families. We also discuss molecular aspects of promoter recognition and epigenetic control of gene expression.

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Nuclear Receptors: One Big Family

Cited by 117 publications

References 50 publications

Dynamic Estrogen Receptor Interactomes Control Estrogen-Responsive Trefoil Factor (TFF) Locus Cell-Specific Activities

Dynamic Estrogen Receptor Interactomes Control Estrogen-Responsive Trefoil Factor (TFF) Locus Cell-Specific Activities

1. Estrogen and Progestin Stimulation of Breast Proliferation

Structural insights into transcription complexes

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