Ligand binding shifts highly mobile RXR to chromatin-bound state in a coactivator-dependent manner as revealed by single cell imaging.
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Tartalom: http://real.mtak.hu/21022/
Archívum: MTA Könyvtár
Gyűjtemény: Status = Published


Type = Article
Cím:
Ligand binding shifts highly mobile RXR to chromatin-bound state in a coactivator-dependent manner as revealed by single cell imaging.
Létrehozó:
Brazda, P.
Krieger, J.
Dániel, Bence
Jonas, D.
Szekeres, T.
Nagy, László
Vámosi, György
Dátum:
2014
Téma:
QH3015 Molecular biology / molekuláris biológia
QH3020 Biophysics / biofizika
Tartalmi leírás:
Retinoid X Receptor (RXR) is a promiscuous nuclear receptor forming heterodimers with several other receptors, which activate different sets of genes. Upon agonist treatment the occupancy of its genomic binding regions increased, but only a modest change in the number of sites was revealed by ChIP-Seq, suggesting a rather static behavior. However, such genome-wide and biochemical approaches do not take into account the dynamic behavior of a transcription factor. Therefore we characterized the nuclear dynamics of RXR during activation in single cells on the sub-second scale using live-cell imaging. By applying FRAP and fluorescence correlation spectroscopy (FCS), techniques with different temporal and spatial resolution, a highly dynamic behavior could be uncovered, which is best described by a two-state model of receptor mobility. In the unliganded state most RXRs belonged to the fast population, leaving approximately 15% for the slow, chromatin bound fraction. Upon agonist treatment, this ratio increased to approximately 43% as a result of an immediate and reversible redistribution. Coactivator binding appears to be indispensable for redistribution and has a major contribution to chromatin association. A nuclear mobility map recorded by light sheet microscopy-FCS shows that the ligand-induced transition from the fast to the slow population occurs throughout the nucleus. Our results support a model in which RXR has a distinct, highly dynamic nuclear behavior and follows hit-and-run kinetics upon activation.
Típus:
Article
PeerReviewed
Formátum:
text
Azonosító:
Brazda, P. and Krieger, J. and Dániel, Bence and Jonas, D. and Szekeres, T. and Nagy, László and Vámosi, György (2014) Ligand binding shifts highly mobile RXR to chromatin-bound state in a coactivator-dependent manner as revealed by single cell imaging. MOLECULAR AND CELLULAR BIOLOGY, 34 (7). pp. 1234-1245. ISSN 0270-7306, ESSN: 1098-5549
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