article · 12/06/2014
Single-molecule tracking in live cells reveals distinct target-search strategies of transcription factors in the nucleus
Résumé
Gene regulation relies on transcription factors (TFs) exploring the nucleus searching their targets. So far, most studies have focused on how fast TFs diffuse, underestimating the role of nuclear architecture. We implemented a single-molecule tracking assay to determine TFs dynamics. We found that c-Myc is a global explorer of the nucleus. In contrast, the positive transcription elongation factor P-TEFb is a local explorer that oversamples its environment. Consequently, each c-Myc molecule is equally available for all nuclear sites while P-TEFb reaches its targets in a position-dependent manner. Our observations are consistent with a model in which the exploration geometry of TFs is restrained by their interactions with nuclear structures and not by exclusion. The geometry-controlled kinetics of TFs target-search illustrates the influence of nuclear architecture on gene regulation, and has strong implications on how proteins react in the nucleus and how their function can be regulated in space and time.
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Izeddin, I., Recamier, V., Bosanac, L., Cisse, I.-I., Boudarene, L., Dugast-Darzacq, C., Proux, F., Benichou, O., Voituriez, R., Bensaude, O., Dahan, M., & Darzacq, X. (2014). Single-molecule tracking in live cells reveals distinct target-search strategies of transcription factors in the nucleus. ELIFE, 3(e02230). https://doi.org/10.7554/eLife.02230@article{Izeddin2014_220,
author = {Izeddin, Ignacio and Recamier, Vincent and Bosanac, Lana and Cisse, Ibrahim I. and Boudarene, Lydia and Dugast-Darzacq, Claire and Proux, Florence and Benichou, Olivier and Voituriez, Raphael and Bensaude, Olivier and Dahan, Maxime and Darzacq, Xavier},
year = {2014},
month = {6},
title = {Single-molecule tracking in live cells reveals distinct target-search strategies of transcription factors in the nucleus},
journal = {ELIFE},
volume = {3},
number = {e02230},
abstract = {Gene regulation relies on transcription factors (TFs) exploring the nucleus searching their targets. So far, most studies have focused on how fast TFs diffuse, underestimating the role of nuclear architecture. We implemented a single-molecule tracking assay to determine TFs dynamics. We found that c-Myc is a global explorer of the nucleus. In contrast, the positive transcription elongation factor P-TEFb is a local explorer that oversamples its environment. Consequently, each c-Myc molecule is equally available for all nuclear sites while P-TEFb reaches its targets in a position-dependent manner. Our observations are consistent with a model in which the exploration geometry of TFs is restrained by their interactions with nuclear structures and not by exclusion. The geometry-controlled kinetics of TFs target-search illustrates the influence of nuclear architecture on gene regulation, and has strong implications on how proteins react in the nucleus and how their function can be regulated in space and time.},
url = {http://www.dx.doi.org/10.7554/eLife.02230},
doi = {10.7554/eLife.02230},
issn = {2050-084X},
}TY - JOUR
AU - Izeddin, Ignacio
AU - Recamier, Vincent
AU - Bosanac, Lana
AU - Cisse, Ibrahim I.
AU - Boudarene, Lydia
AU - Dugast-Darzacq, Claire
AU - Proux, Florence
AU - Benichou, Olivier
AU - Voituriez, Raphael
AU - Bensaude, Olivier
AU - Dahan, Maxime
AU - Darzacq, Xavier
PY - 2014
DA - 2014/06/12
TI - Single-molecule tracking in live cells reveals distinct target-search strategies of transcription factors in the nucleus
JO - ELIFE
VL - 3
IS - e02230
SN - 2050-084X
AB - Gene regulation relies on transcription factors (TFs) exploring the nucleus searching their targets. So far, most studies have focused on how fast TFs diffuse, underestimating the role of nuclear architecture. We implemented a single-molecule tracking assay to determine TFs dynamics. We found that c-Myc is a global explorer of the nucleus. In contrast, the positive transcription elongation factor P-TEFb is a local explorer that oversamples its environment. Consequently, each c-Myc molecule is equally available for all nuclear sites while P-TEFb reaches its targets in a position-dependent manner. Our observations are consistent with a model in which the exploration geometry of TFs is restrained by their interactions with nuclear structures and not by exclusion. The geometry-controlled kinetics of TFs target-search illustrates the influence of nuclear architecture on gene regulation, and has strong implications on how proteins react in the nucleus and how their function can be regulated in space and time.
DO - 10.7554/eLife.02230
UR - http://www.dx.doi.org/10.7554/eLife.02230
ER -