Distinctly Different Dynamics and Kinetics of Two Steroid Receptors at the Same Response Elements in Living Cells

Nenseth, Hatice Zeynep; Dezitter, Xavier; Tesikova, Martina; Mueller, Florian; Klokk, Tove Irene; Hager, Gordon L.; Saatcioglu, Fahri

doi:10.1371/journal.pone.0105204

Cited by 13 publications

(14 citation statements)

References 49 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Within the nucleus, GFP-AR showed a striking transition from no detectable correlation before Cl-4AS-1 treatment, suggesting the majority of GFP-AR to be diffusive, to long, consistent correlation after adding ligand. This AR agonist-induced binding in the nucleus has been reported previously in other studies 19 20 37 . Within the cytoplasm, GFP-AR showed the decreased diffusion after Cl-4AS-1 treatment.…”

Section: Resultssupporting

confidence: 89%

“…Recently developed microscopy techniques have greatly improved our understanding of nuclear receptor kinetics, including AR 4 5 16 17 18 19 20 . A common approach to probing molecular dynamics is through fluorescence recovery after photo-bleaching (FRAP) 18 19 20 , which measures a fluorescent particle’s diffusion coefficient by selectively bleaching a cellular region and observing the return of fluorescence to that region. However, due to the large number of experimental variables, the variety of analytical approaches and the inaccuracy of FRAP at short time intervals, the results of these quantifications have failed to provide a consistent view on transcription factor mobility and the nature and timing of their interactions with DNA 21 .…”

mentioning

confidence: 99%

See 1 more Smart Citation

Intracellular kinetics of the androgen receptor shown by multimodal Image Correlation Spectroscopy (mICS)

Chiu

Patsch²,

Cutrale

et al. 2016

Sci Rep

View full text Add to dashboard Cite

The androgen receptor (AR) pathway plays a central role in prostate cancer (PCa) growth and progression and is a validated therapeutic target. In response to ligand binding AR translocates to the nucleus, though the molecular mechanism is not well understood. We therefore developed multimodal Image Correlation Spectroscopy (mICS) to measure anisotropic molecular motion across a live cell. We applied mICS to AR translocation dynamics to reveal its multimodal motion. By integrating fluorescence imaging methods we observed evidence for diffusion, confined movement, and binding of AR within both the cytoplasm and nucleus of PCa cells. Our findings suggest that in presence of cytoplasmic diffusion, the probability of AR crossing the nuclear membrane is an important factor in determining the AR distribution between cytoplasm and the nucleus, independent of functional microtubule transport. These findings may have implications for the future design of novel therapeutics targeting the AR pathway in PCa.

show abstract

Section: Resultssupporting

confidence: 89%

mentioning

confidence: 99%

Intracellular kinetics of the androgen receptor shown by multimodal Image Correlation Spectroscopy (mICS)

Chiu

Patsch²,

Cutrale

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…These differences of residence at the MMTV enhancer array are compound effects of DNA binding as well as differential effects of other binding transcription factors, histon modifiers, and chromatin remodeling complexes [86, 87]. …”

Section: Cooperativity With Other Transcription Factorsmentioning

confidence: 99%

Comparing the rules of engagement of androgen and glucocorticoid receptors

Claessens

Joniau

Helsen

2017

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Despite the diverse physiological activities of androgens and glucocorticoids, the corresponding receptors are very close members of the nuclear-receptor super family. Their action mechanisms show striking similarities, since both receptors recognize very similar DNA-response elements and recruit the same coactivators to their target genes. The specificity of the responses lies mainly in the tissue-specific expression of the receptors and in their ligand specificity. In cells, where both receptors are expressed, the mechanisms leading to the difference in target genes are less obvious. They lie in part in subtle variations of the DNA-binding sites, in cooperativity with other transcription factors and in differential allosteric signals from the DNA and ligand to other receptor domains. We will highlight the different suggestions that might explain the DNA sequence selectivity and will compare the possible allosteric routes between the response elements and the different functions in the transactivation process. The interplay of androgen and glucocorticoid receptors is also highly relevant in clinical settings, where both receptors are therapeutically targeted. We will discuss the possibility that the glucocorticoid and androgen receptors can play partially redundant roles in castration-resistant prostate cancer.

show abstract

“…Cells-GFP-GR binds to and activates transcription from the same HREs within the MMTV array as GFP-AR (4,7,18). The unexpected results that are summarized above for GFP-AR prompted us to examine if these findings may also apply to GFP-GR.…”

Section: Hdac Inhibitors Do Not Affect Gfp-gr Mobility At Hres In Livingmentioning

confidence: 94%

Divergent Binding and Transactivation by Two Related Steroid Receptors at the Same Response Element

Tesikova

Dezitter

Nenseth

et al. 2016

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Transcription factor (TF) recruitment to chromatin is central to activation of transcription. TF-chromatin interactions are highly dynamic, which are evaluated by recovery half time (t 1/2 ) in seconds, determined by fluorescence recovery experiments in living cells, and chromatin immunoprecipitation (ChIP) analysis, measured in minutes. These two states are related: the larger the t 1/2, the longer the ChIP occupancy resulting in increased transcription. Here we present data showing that this relationship does not always hold. We found that histone deacetylase inhibitors (HDACis) significantly increased t 1/2 of green fluorescent protein (GFP) fused androgen receptor (AR) on a tandem array of positive hormone response elements (HREs) in chromatin. This resulted in increased ChIP signal of GFP-AR. Unexpectedly, however, transcription was inhibited. In contrast, the GFP-fused glucocorticoid receptor (GR), acting through the same HREs, displayed a profile consistent with current models. We provide evidence that these differences are mediated, at least in part, by HDACs. Our results provide insight into TF action in living cells and show that very closely related TFs may trigger significantly divergent outcomes at the same REs.

show abstract

Distinctly Different Dynamics and Kinetics of Two Steroid Receptors at the Same Response Elements in Living Cells

Cited by 13 publications

References 49 publications

Intracellular kinetics of the androgen receptor shown by multimodal Image Correlation Spectroscopy (mICS)

Intracellular kinetics of the androgen receptor shown by multimodal Image Correlation Spectroscopy (mICS)

Comparing the rules of engagement of androgen and glucocorticoid receptors

Divergent Binding and Transactivation by Two Related Steroid Receptors at the Same Response Element

Contact Info

Product

Resources

About