Functional Imaging of Transcription, Institut de Biologie de l’Ecole Normale Supérieure (IBENS), Inserm U1024, and CNRS UMR 8197, Paris, France; Laboratoire Kastler Brossel, CNRS UMR 8552, Departement de Physique et Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Paris, France
Vincent Récamier
Functional Imaging of Transcription, Institut de Biologie de l’Ecole Normale Supérieure (IBENS), Inserm U1024, and CNRS UMR 8197, Paris, France
Lana Bosanac
Functional Imaging of Transcription, Institut de Biologie de l’Ecole Normale Supérieure (IBENS), Inserm U1024, and CNRS UMR 8197, Paris, France; Transcription Imaging Consortium, Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, United States
Ibrahim I Cissé
Functional Imaging of Transcription, Institut de Biologie de l’Ecole Normale Supérieure (IBENS), Inserm U1024, and CNRS UMR 8197, Paris, France; Laboratoire Kastler Brossel, CNRS UMR 8552, Departement de Physique et Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Paris, France
Lydia Boudarene
Functional Imaging of Transcription, Institut de Biologie de l’Ecole Normale Supérieure (IBENS), Inserm U1024, and CNRS UMR 8197, Paris, France; Laboratoire Kastler Brossel, CNRS UMR 8552, Departement de Physique et Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Paris, France; Université Paris Diderot, Paris, France
Claire Dugast-Darzacq
Functional Imaging of Transcription, Institut de Biologie de l’Ecole Normale Supérieure (IBENS), Inserm U1024, and CNRS UMR 8197, Paris, France; Université Paris Diderot, Paris, France
Florence Proux
Functional Imaging of Transcription, Institut de Biologie de l’Ecole Normale Supérieure (IBENS), Inserm U1024, and CNRS UMR 8197, Paris, France
Olivier Bénichou
Laboratoire de Physique Théorique de la Matière Condensée, CNRS UMR 7600, Université Pierre et Marie Curie, Paris, France
Raphaël Voituriez
Laboratoire de Physique Théorique de la Matière Condensée, CNRS UMR 7600, Université Pierre et Marie Curie, Paris, France
Olivier Bensaude
Cell Biology of Transcription, Institut de Biologie de l'École Normale Supérieure (IBENS) CNRS UMR 8197, Paris, France
Maxime Dahan
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; Laboratoire Physico-Chimie, Institut Curie, CNRS UMR 168, Paris, France
Xavier Darzacq
Functional Imaging of Transcription, Institut de Biologie de l’Ecole Normale Supérieure (IBENS), Inserm U1024, and CNRS UMR 8197, Paris, France; Transcription Imaging Consortium, Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, United States
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.
