Articles in 2015

PRDM16 activates brown adipose-selective genes through direct interaction with the Mediator complex subunit MED1 at enhancer regions and the regulation of chromatin architecture.

Transcription of eukaryotic protein-coding genes requires the assembly of a conserved initiation complex at promoter DNA. Structural information on this complex, which comprises RNA polymerase II and the general transcription factors, is beginning to reveal the mechanisms underlying the initial steps of transcription, such as the recognition and opening of promoter DNA.

RNA polymerase II (Pol II) is globally regulated by Mediator, a large, conformationally flexible protein complex with a variable subunit composition. These biochemical characteristics are fundamental for the ability of Mediator to control processes involved in transcription, including the organization of chromatin architecture and the regulation of Pol II pre-initiation, initiation, re-initiation, pausing and elongation.

Pausing of RNA polymerase II (Pol II) in promoter-proximal regions and its release to initiate productive elongation are key steps in the regulation of transcription, and involve many factors. Evidence is now emerging that transcriptional elongation is highly dynamic. Elongation rates vary between genes and across the length of a gene, affecting splicing, termination and genome stability.

DNA topoisomerase 1 mediates single-strand nicks to relieve the inhibitory effect of DNA supercoiling on enhancer-dependent transcription.

Access of RNA polymerase II to DNA is regulated by the ordered disassembly of nucleosomes and by histone exchange. Chromatin modifications, chromatin remodellers, histone chaperones and histone variants control nucleosomal dynamics, and dysregulation of these components results in aberrant transcription.

Transcription termination has a central role in regulating gene expression, maintaining the stability of the transcriptome and controlling pervasive transcription. New insights have recently been gained into the molecular basis of termination and the timely and efficient dismantling of elongation complexes at mRNA-coding and non-coding RNA loci.

Many gene expression patterns are dictated by enhancers. Mammalian genomes contain millions of potential enhancers, but only a small subset of them is active in any cell type. Emerging data uncover how cell type-specific enhancer function is established, including the involvement of higher-order genomic organization in the process.

Robert Grosse discusses how optogenetic strategies have the potential to advance our understanding of protein function and localization in individual living cells.

A new study shows that phosphorylation regulates the folding, and thus biological function, of the intrinsically disordered protein 4E-BP2.

Kapitein and colleagues have used an optically controlled system that couples organelles and motor proteins to study the dynamics and roles of organelle transport.

A robust method to induce primordial germ cells from human pluripotent stem cells has been developed, highlighting the importance of SOX17 in the specification of the human germline.

Two studies have determined the molecular mechanisms that underlie a specific clathrin-independent pathway for the internalization of activated surface receptors and bacterial toxins.

The RNA-binding protein Elav is recruited in the fruit fly to promoter regions, possibly by paused RNA polymerase II, to promote alternative polyadenylation.

Considerable progress has been made in the past few years in our ability to visualize the structure of G protein-coupled receptors (GPCRs) and their signalling complexes. This is due to a series of technical improvements in areas such as protein engineering, lipidic cubic phase-based crystallization and microfocus synchrotron beamlines.

The anaphase-promoting complex (also known as the cyclosome) is an E3 ubiquitin ligase that has a crucial function in the regulation of mitosis, particularly during anaphase and mitotic exit. Its activity is tightly controlled by several factors to ensure the timely degradation of key mitotic regulators and thus the proper progression of mitotic events.

Chromatin decondensation is sufficient to induce the relocation of loci from the periphery to the centre of nuclei.