Single-molecule tracking in live cells reveals distinct target-search strategies of transcription factors in the nucleus

eLife

Vincent Récamier¹  Raphaël Voituriez¹  Florence Proux¹  Lydia Boudarene²  Olivier Bensaude³  Xavier Darzacq³  Ignacio Izeddin⁴  Lana Bosanac⁴  Claire Dugast-Darzacq⁴  Maxime Dahan⁴  Ibrahim I Cissé⁴  Olivier Bénichou⁴ 

[1] Laboratoire Kastler Brossel, CNRS UMR 8552, Departement de Physique et Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Paris, France;Transcription Imaging Consortium, Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, United States;Université Paris Diderot, Paris, France;Functional Imaging of Transcription, Institut de Biologie de l’Ecole Normale Supérieure (IBENS), Inserm U1024, and CNRS UMR 8197, Paris, France;

关键词: single-molecule tracking;    transcription regulation;    target search;    nuclear organization;   

DOI  :  10.7554/eLife.02230

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown