Reviews & Analysis

Nucleosome positioning is crucial for gene expression and other DNA-related processes. In this Review, the authors consider mechanisms by which the genomic pattern of nucleosome positioning is achieved and conclude that nucleosome positioning is determined by the combined effects of several factors including DNA sequence, DNA-binding proteins, nucleosome remodelers and the transcription machinery.

A fundamental property of genomes is their topological organization in three-dimensional space in the cell nucleus. New imaging technologies and genome-wide biochemical approaches combined with functional data are starting to reveal the functional implications of genome topology, as discussed in this Review, and will enable a better understanding of how genome organization influences gene function, and vice versa.

Long noncoding RNAs (lncRNAs) fulfill a variety of regulatory roles in gene expression, which are dictated by their RNA structure, chemistry and modular domain structure. In this Review, the focus is on the well-characterized ability for lncRNAs to function as epigenetic modulators as part of a broad epigenetic regulatory network.

DNA methylation is an epigenetic mark that is erased in the early embryo and then re-established at the time of implantation. In this Review, dynamics of DNA methylation during normal development in vivo are discussed, starting from fertilization through embryogenesis and postnatal growth, as well as abnormal methylation changes that occur in cancer.

Self-assembly of the COPII coat proteins Sec13 and Sec31 creates a spherical cage that drives vesicle formation from the endoplasmic reticulum. A multipronged approach now provides a convincing pseudoatomic model of the assembled cage that sharpens our understanding of the architecture, contact sites and flexibility of this remarkable structure.

Direct time-resolved single-molecule observations of promoter search by Escherichia coli RNA polymerase indicate no evidence of facilitated diffusion, according to a new report.

Three recent studies converged on a specific protein-protein interface between TPP1 and telomerase as being crucial for the regulation of both telomerase recruitment and processivity in mammalian cells. An equivalent interaction appears to exist in budding yeast, making this a nearly universal means of telomerase regulation.

Chromatin-remodeling enzymes use the energy from ATP hydrolysis to mobilize, disrupt or change the histone composition of nucleosomes, facilitating nearly every nuclear event. Two recent studies indicate that remodeling enzymes harness the power of an ancient constitutively active DNA translocase and that different remodeling enzymes may use specialized coupling domains that communicate the presence of nucleosomal epitopes to regulate translocase and remodeling activity.

The Sixth International Conference on Hsp90 in 2012 revealed new functions of this key molecular chaperone. Attendees of the meeting at Les Diablerets, Switzerland, addressed new discoveries about Hsp90 and its cochaperones.

Peptide loading of major histocompatibility complex (MHC) class II molecules in the endosomes and lysosomes of antigen-presenting cells is catalyzed by human leukocyte antigen-DM (HLA-DM) and modulated by HLA-DO. In a structural study in this issue, Guce et al. show that HLA-DO is an MHC class II mimic and functions as a competitive and essentially irreversible inhibitor of HLA-DM activity, thereby inhibiting MHC class II antigen presentation.

Nucleosome assembly is crucial for the maintenance of genome stability and epigenetic information and is aided by histone chaperones. This Review discusses recent insights into the mechanisms and roles of histone chaperones in regulating nucleosome assembly and how alterations in nucleosome-assembly factors may be implicated in human diseases.