Live-cell imaging has revealed unexpected features of gene expression. Here using improved single-molecule RNA microscopy, we show that synthesis of HIV-1 RNA is achieved by groups of closely spaced polymerases, termed convoys, as opposed to single isolated enzymes. Convoys arise by a Mediator-dependent reinitiation mechanism, which generates a transient but rapid succession of polymerases initiating and escaping the promoter. During elongation, polymerases are spaced by few hundred nucleotides, and physical modelling suggests that DNA torsional stress may maintain polymerase spacing. We additionally observe that the HIV-1 promoter displays stochastic fluctuations on two time scales, which we refer to as multi-scale bursting. Each time scale is regulated independently: Mediator controls minute-scale fluctuation (convoys), while TBP-TATA-box interaction controls sub-hour fluctuations (long permissive/non-permissive periods). A cellular promoter also produces polymerase convoys and displays multi-scale bursting. We propose that slow, TBP-dependent fluctuations are important for phenotypic variability of single cells.

Statistical entropy was introduced by Shannon as a basic concept in information theory measuring the average missing information in a random source. Extended into an entropy rate, it gives bounds in coding and compression theorems. In this paper, I describe how statistical entropy and entropy rate relate to other notions of entropy that are relevant to probability theory (entropy of a discrete probability distribution measuring its unevenness), computer sciences (algorithmic complexity), the ergodic theory of dynamical systems (Kolmogorov–Sinai or metric entropy) and statistical physics (Boltzmann entropy). Their mathematical foundations and correlates (the entropy concentration, Sanov, Shannon–McMillan–Breiman, Lempel–Ziv and Pesin theorems) clarify their interpretation and offer a rigorous basis for maximum entropy principles. Although often ignored, these mathematical perspectives give a central position to entropy and relative entropy in statistical laws describing generic collective behaviours, and provide insights into the notions of randomness, typicality and disorder. The relevance of entropy beyond the realm of physics, in particular for living systems and ecosystems, is yet to be demonstrated.

While statistical mechanics describe the equilibrium state of systems with many degrees of freedom, and dynamical systems explain the irregular evolution of systems with few degrees of freedom, new tools are needed to study the evolution of systems with many degrees of freedom. This book presents the basic aspects of chaotic systems, with emphasis on systems composed by huge numbers of particles. Firstly, the basic concepts of chaotic dynamics are introduced, moving on to explore the role of ergodicity and chaos for the validity of statistical laws, and ending with problems characterized by the presence of more than one significant scale. Also discussed is the relevance of many degrees of freedom, coarse graining procedure, and instability mechanisms in justifying a statistical description of macroscopic bodies. Introducing the tools to characterize the non asymptotic behaviors of chaotic systems, this text will interest researchers and graduate students in statistical mechanics and chaos.

In higher organisms, all cells share the same genome, but every cell expresses only a limited and specific set of genes that defines the cell type. During cell division, not only the genome, but also the cell type is inherited by the daughter cells. This intriguing phenomenon is achieved by a variety of processes that have been collectively termed epigenetics: the stable and inheritable changes in gene expression patterns. This article reviews the extremely rich and exquisitely multiscale physical mechanisms that govern the biological processes behind the initiation, spreading, and inheritance of epigenetic states. These include not only the changes in the molecular properties associated with the chemical modifications of DNA and histone proteins, such as methylation and acetylation, but also less conventional changes, typically in the physics that governs the three-dimensional organization of the genome in cell nuclei. Strikingly, to achieve stability and heritability of epigenetic states, cells take advantage of many different physical principles, such as the universal behavior of polymers and copolymers, the general features of dynamical systems, and the electrostatic and mechanical properties related to chemical modifications of DNA and histones. By putting the complex biological literature in this new light, the emerging picture is that a limited set of general physical rules play a key role in initiating, shaping, and transmitting this crucial “epigenetic landscape.” This new perspective not only allows one to rationalize the normal cellular functions, but also helps to understand the emergence of pathological states, in which the epigenetic landscape becomes dysfunctional.