title: Intra-nuclear mobility and target search mechanisms of transcription factors: a single-molecule perspective on gene expression.
abstract: Precise expression of specific genes in time and space is at the basis of cellular viability as well as correct development of organisms. Understanding the mechanisms of gene regulation is fundamental and still one of the great challenges for biology. Gene expression is regulated also by specific transcription factors that recognize and bind to specific DNA sequences. Transcription factors dynamics, and especially the way they sample the nucleoplasmic space during the search for their specific target in the genome, are a key aspect for regulation and it has been puzzling researchers for forty years. The scope of this review is to give a state-of-the-art perspective over the intra-nuclear mobility and the target search mechanisms of specific transcription factors at the molecular level. Going through the seminal biochemical experiments that have raised the first questions about target localization and the theoretical grounds concerning target search processes, we describe the most recent experimental achievements and current challenges in understanding transcription factors dynamics and interactions with DNA using in vitro assays as well as in live prokaryotic and eukaryotic cells. This article is part of a Special Issue entitled: Nuclear Transport and RNA Processing.
authors.affiliation: Institut de Biologie de l'Ecole normale supérieure (IBENS), CNRS UMR 8197, Ecole normale supérieure, 46, Rue d'Ulm, 75005 Paris, France. normanno@biologie.ens.fr
authors.forename: Davide
authors.initials: D
authors.lastname: Normanno
authors.forename: Maxime
authors.initials: M
authors.lastname: Dahan
authors.forename: Xavier
authors.initials: X
authors.lastname: Darzacq
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival; D004247:DNA / Q000235:genetics / Q000378:metabolism; D056890:Eukaryota / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D006801:Humans; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors; D004247:DNA