Chromatin is the substrate of all gene-regulatory processes in eukaryotic cells. Faithful transcription relies on finely tuned chromatin-remodelling mechanisms that enable temporal access to – or the blocking of – DNA critical sequences, such as gene promoters. A specific set of proteins, chromatin-remodelling factors, is dedicated to this task. Put in brief, they actively modulate chromatin structure by dynamically changing the location of nucleosomes, affecting both small-scale and large-scale chromatin structure.
The understanding of chromatin-remodelling mechanisms poses a challenge to molecular biology and biophysics, to experiment and theory. There are several reasons for this. Remodellers come in different families with different functions. They are multiprotein complexes for which structural information is difficult to obtain and hence still scarce. Their interactions with nucleosomes are biochemical and mechanical. They are molecular motors consuming ATP. Modern imaging techniques, single-molecule experiments and mathematical modeling have therefore recently joined biochemistry and molecular biology techniques in a common effort to decipher the chromatin-remodelling rules.
The aim of this minireview series is to provide an introductory overview of the different mechanisms used by some of these factors to regulate DNA access to the transcription machinery and of the current methods used to gather this information. It arises from a workshop recently dedicated to this subject (http://www.iri.cnrs.fr/doc/chromatin_days_2010/), which brought together a select group of international experts for a focused exchange on the current developments in this field. This occasion allowed us to invite the participants to write four minireviews, each of which covers a major approach currently employed to understand chromatin remodelling: (a) in the first minireview, Flaus and Owen-Hughes give an overview of biochemical approaches aimed at identifying the various remodelling machines families and deciphering their mechanisms, (b) in the second minireview, Lavelle et al. show how single-molecule techniques have recently complemented biochemical techniques to investigate the action of remodellers and other ATP-consuming molecular motors interacting with DNA, (c) in the third minireview, Erdel and Rippe discuss in vivo approaches aimed at understanding how imitation switch (ISWI) chromatin remodellers operate in mammalian cells and (d) in the fourth minireview, Blossey and Schiessel discuss the current understanding of theoretical biophysics of nucleosome mechanics and the effects of thermal energy, applied forces and ATP-driven remodelling processes.
We hope that this minireview collection will help both the uninitiated and the expert: the former with an entry point to a highly dynamic, but admittedly complex field of research, and the latter with an opportunity to take a quick glance at the viewpoints advocated by the researchers from the different disciplines that have contributed. We are both convinced that cracking the problem of chromatin remodelling will be considered in the future as a prime example of an interdisciplinary effort on an important biological problem.
[ Christophe Lavelle is a research scientist at the CNRS (French National Scientific Research Agency) in Paris, France (firstname.lastname@example.org). After obtaining a Masters degree in Physics, he obtained a PhD in Molecular Biophysics and spent 6 years as a postdoctoral researcher in different laboratories, studying chromatin structure and dynamics through various approaches. His current research focuses on DNA topology and mechanistic aspects of transcription, using a combination of molecular biology and single molecule techniques. He also teaches in several universities, mainly biophysics but also food science. ]
[ Ralf Blossey is a research director at the CNRS (French National Scientific Research Agency) in Lille, France (email@example.com). He obtained his PhD in Theoretical Physics at the University of Düsseldorf, Germany. After postdoctoral studies at the University of Washington in Seattle (USA), and at the Catholic University of Leuven (Belgium), he started a research group at the interface between soft matter physics and bioinformatics at the Interdisciplinary Research Institute (IRI) in Lille. Among his research topics are the dynamics of unstable polymer films, DNA and protein interactions, and the dynamics of signaling and transcription networks. ]