Összesen 2 találat.


001-es BibID:BIBFORM049213
Első szerző:Brázda Péter (biológus, angol-magyar szakfordító)
Cím:Ligand binding shifts highly mobile RXR to chromatin-bound state in a coactivator-dependent manner as revealed by single cell imaging / Peter Brazda, Jan Krieger, Bence Daniel, David Jonas, Tibor Szekeres, Jörg Langowski, Katalin Tóth, Laszlo Nagy, György Vámosi
Megjegyzések: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 ~15% for the slow, chromatin bound fraction. Upon agonist treatment, this ratio increased to ~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.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
nuclear receptor
Megjelenés:Molecular and Cellular Biology. - 34 : 7 (2014), p. 1234-1245. -
További szerzők:Krieger, Jan W. Dániel Bence (1987-) (molekuláris biológus) Jonás Dávid Szekeres Tibor (1984-) (molekuláris biológus) Langowski, Jörg Tóth Katalin Ágnes (1977-) (biokémikus, molekuláris biológus) Nagy László (1966-) (molekuláris sejtbiológus, biokémikus) Vámosi György (1967-) (biofizikus)
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat


001-es BibID:BIBFORM048680
Első szerző:Brázda Péter (biológus, angol-magyar szakfordító)
Cím:Live-cell fluorescence correlation spectroscopy dissects the role of coregulator exchange and chromatin binding in retinoic acid receptor mobility / Peter Brazda, Tibor Szekeres, Balázs Bravics, Katalin Tóth, György Vámosi, László Nagy
Megjegyzések:The retinoic acid receptor (RAR) is a member of the nuclear receptor superfamily. This ligand-inducible transcription factor binds to DNA as a heterodimer with the retinoid X receptor (RXR) in the nucleus. The nucleus is a dynamic compartment and live-cell imaging techniques make it possible to investigate transcription factor action in real-time. We studied the diffusion of EGFP-RAR by fluorescence correlation spectroscopy (FCS) to uncover the molecular interactions determining receptor mobility. In the absence of ligand, we identified two distinct species with different mobilities. The fast component has a diffusion coefficient of D(1)=1.8-6.0 ?m(2)/second corresponding to small oligomeric forms, whereas the slow component with D(2)=0.05-0.10 ?m(2)/second corresponds to interactions of RAR with the chromatin or other large structures. The RAR ligand-binding-domain fragment also has a slow component, probably as a result of indirect DNA-binding through RXR, with lower affinity than the intact RAR-RXR complex. Importantly, RAR-agonist treatment shifts the equilibrium towards the slow population of the wild-type receptor, but without significantly changing the mobility of either the fast or the slow population. By using a series of mutant forms of the receptor with altered DNA- or coregulator-binding capacity we found that the slow component is probably related to chromatin binding, and that coregulator exchange, specifically the binding of the coactivator complex, is the main determinant contributing to the redistribution of RAR during ligand activation.
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
transcription regulation
nuclear receptor
fluorescence correlation spectroscopy
Megjelenés:Journal of Cell Science. - 124 : 21 (2011), p. 3631-3642. -
További szerzők:Szekeres Tibor (1984-) (molekuláris biológus) Bravics Balázs Tóth Katalin Ágnes (1977-) (biokémikus, molekuláris biológus) Vámosi György (1967-) (biofizikus) Nagy László (1966-) (molekuláris sejtbiológus, biokémikus)
Pályázati támogatás:TÁMOP-4.2.1/B-09/1/KONV-2010-0007
Fehérje-fehérje kölcsönhatások limfociták membránjában és a sejtmagban
Internet cím:Szerző által megadott URL
Intézményi repozitóriumban (DEA) tárolt változat
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