The Ligand Binding Domain Controls Glucocorticoid Receptor Dynamics Independent of Ligand Release

Meijsing, Sebastiaan H.; Elbi, Cem; Luecke, Hans; Hager, Gordon L.; Yamamoto, Keith R.

doi:10.1128/mcb.01570-06

Cited by 51 publications

(45 citation statements)

References 43 publications

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“…Since the observed cycles were typically in the order of tens of minutes these data initiated discussion on the interpretation of many of the preceding FRAP experiments on nuclear receptors which suggested a much shorter binding time in the order of tens of seconds rather than minutes (e.g. McNally et al 2000;Farla et al 2004Farla et al , 2005Schaaf and Cidlowski 2003;Rayasam et al 2005;Marcelli et al 2006;Klokk et al 2007;Meijsing et al 2007). …”

Section: How Do Nuclear Proteins Bind Their Targets?mentioning

confidence: 98%

Nuclear proteins: finding and binding target sites in chromatin

et al. 2010

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Fluorescent protein labelling, as well as impressive progress in live cell imaging have revolutionised the view on how essential nuclear functions like gene transcription regulation and DNA repair are organised. Here, we address questions like how DNAinteracting molecules find and bind their target sequences in the vast amount of DNA. In addition, we discuss methods that have been developed for quantitative analysis of data from fluorescence recovery after photobleaching experiments (FRAP).

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Section: How Do Nuclear Proteins Bind Their Targets?mentioning

confidence: 98%

Nuclear proteins: finding and binding target sites in chromatin

et al. 2010

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“…Estrogen receptor binds a diverse set of sites and, based on the sequence of that site, interacts selectively with cofactors (29). Likewise, glucocorticoid receptor transcriptional output and structure are influenced by the exact sequence of the bound glucocorticoid response element (2,30). Previous work on nuclear receptors used a combination of natural and synthetic ligands.…”

Section: Discussionmentioning

confidence: 99%

Single nucleotide in the MTF-1 binding site can determine metal-specific transcription activation

Sims

Chirn

Marr

2012

Proc. Natl. Acad. Sci. U.S.A.

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Cells respond to changes in environment by shifting their gene expression profile to deal with the new conditions. The cellular response to changes in metal homeostasis is an important example of this. Transition metals such as iron, zinc, and copper are essential micronutrients but other metals such as cadmium are simply toxic. The cell must maintain metal concentrations in a window that supports efficient metabolic function but must also protect against the damaging effects of high concentrations of these metals. One way a cell regulates metal homeostasis is to control genes involved in metal mobilization and storage. Much of this regulation occurs at the level of transcription and the protein most responsible for this is the conserved metal responsive transcription factor 1 (MTF-1). Interestingly, the nature of the changes in the gene expression profile depends on the type of exposure. The cell somehow senses the kind of the metal challenge and responds appropriately. We have been using the Drosophila system to try to understand the mechanism of this metal discrimination. Using genome-wide mapping of MTF-1 binding under different metal stresses we find that, surprisingly, MTF-1 chooses different DNA binding sites depending on the specific nature of the metal insult. We also find that the type of binding site chosen is an important component of the capability to induce the metal-specific transcription activation.heavy metal | MED26 D NA recognition by sequence-specific DNA binding transcription factors is the basic mechanism that links the cisregulatory information encoded in the genome with transcriptional control of gene expression. Although it is the DNA binding domain of these factors that dictates the sequence element bound by the protein, it is now clear that, at least for some factors, the DNA sequence of the binding site itself can influence the activation potential of the transcription factor (1, 2). Clearly the process of reading the genome and activating transcription is more intricate than a simple DNA binding event.Some transcription factors respond to signaling events and activate the transcription of different sets of genes in a signalspecific manner. The cellular response to changes in metal homeostasis is one example of this observation. The major transcription factor involved in metal homeostasis is the metal responsive element (MRE) binding transcription factor-1 (MTF-1) (for a recent review, see ref.3). MTF-1 is required for both constitutive and metal inducible transcription of some genes; it is also required for activated transcription of at least one gene in low metal conditions (4, 5). Thus, it responds to both excess and limiting metal conditions by activating different sets of genes.

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“…As discussed above, the possibility that a large fraction of DNAbound TR-containing complexes are unable to transactivate is consistent with the frequent presence of TRBS next to genes that are not regulated by T3. This situation would be another illustration of the allosteric properties of the DNA/nuclear receptors/ ligand/cofactor complexes, where the interface between DNA and nuclear receptors can influence not only the stability of the interaction with DNA but also the recruitment of coactivators and corepressors (10,(46)(47)(48). A recent analysis of regulation by T3 of the TSHβ gene in a pituitary cell line confirmed this general hypothesis, providing a clear example where both receptors can bind proximal sequences, with only TRβ1 being able to regulate transcription (49).…”

Section: Mechanisms Of Tr-mediated Transcriptional Regulationmentioning

confidence: 99%

Genome-wide analysis of thyroid hormone receptors shared and specific functions in neural cells

Chatonnet

Guyot

Galand

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

109

100

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TRα1 and TRβ1, the two main thyroid hormone receptors in mammals, are transcription factors that share similar properties. However, their respective functions are very different. This functional divergence might be explained in two ways: it can reflect different expression patterns or result from different intrinsic properties of the receptors. We tested this second hypothesis by comparing the repertoires of 3,3′,5-triiodo-L-thyronine (T3)-responsive genes of two neural cell lines, expressing either TRα1 or TRβ1. Using transcriptome analysis, we found that a substantial fraction of the T3 target genes display a marked preference for one of the two receptors. So when placed alone in identical situations, the two receptors have different repertoires of target genes. Chromatin occupancy analysis, performed at a genome-wide scale, revealed that TRα1 and TRβ1 cistromes were also different. However, receptor-selective regulation of T3 target genes did not result from receptor-selective chromatin occupancy of their promoter regions. We conclude that modification of TRα1 and TRβ1 intrinsic properties contributes in a large part to the divergent evolution of the receptors' function, at least during neurodevelopment.

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The Ligand Binding Domain Controls Glucocorticoid Receptor Dynamics Independent of Ligand Release

Cited by 51 publications

References 43 publications

Nuclear proteins: finding and binding target sites in chromatin

Nuclear proteins: finding and binding target sites in chromatin

Single nucleotide in the MTF-1 binding site can determine metal-specific transcription activation

Genome-wide analysis of thyroid hormone receptors shared and specific functions in neural cells

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