Articles in 2013

Nucleosome-remodeling factors are instrumental in assembling and disassembling nucleosomes and moving nucleosomes along DNA in a process called nucleosome sliding. This Review summarizes recent progress in understanding of the basic nucleosome sliding mechanism and the interplay of the ATPase and accessory domains in optimizing and regulating nucleosome sliding.

Although histone H3 Lys4 (H3K4) methylation is widely associated with gene activation, direct evidence for its causal role in transcription is lacking. New studies with the histone methyltransferase MLL2 in a cell-free transcription system now establish a direct causal role for MLL2-mediated H3K4 methylation in transcription and identify AKAP95 as a new modulator of H3K4 methylation.

How the activity of transposable elements is regulated is not well understood. A new study now shows that the Microprocessor complex, which is required for microRNA biogenesis, also recognizes and binds RNAs derived from human LINE-1, Alu and SVA retrotransposons and that it acts as a post-transcriptional repressor of mammalian retrotransposons in vivo.

Ligand-gated ion channels are susceptible to inactivation upon prolonged exposure to their ligand, a process known as desensitization. A sodium-binding pocket within the KAR-type glutamate receptor GluK2 is now shown to have a crucial role in this process, as desensitization is shown to occur only when the ligand is bound without cation pocket occupancy.

The deubiquitinating enzyme OTUB1 binds charged E2 intermediates and prevents ubiquitin transfer. OTUB1 can also bind uncharged E2, and this interaction is now shown to stimulate OTUB1's deubiquitination activity. Thus, OTUB1–E2 complexes might regulate levels of ubiquitin conjugation in response to available free ubiquitin and the ratio of charged to uncharged E2.

Acetylation of the Sir3 N terminus is important for transcriptional silencing in budding yeast and is thought to promote binding of the Sir3 BAH domain to the nucleosome. Structural and biochemical analyses now demonstrate that the acetylated Sir3 N terminus does not interact with the nucleosome directly but instead stabilizes a nucleosome-binding loop in the BAH domain.

N-terminal acetylation of Sir3 is essential for heterochromatin establishment and maintenance in yeast, but its mechanism of action is unknown. The crystal structure of the N-terminally acetylated BAH domain of Sir3 bound to the nucleosome core particle revealed that N-terminal acetylation stabilizes the interaction of Sir3 with the nucleosome.

Embryonic stem cells (ESCs) possess a unique chromatin landscape in which 'bivalent' domains of trimethylated histone H3 Lys4 (H3K4me3) and Lys27 (H3K27me3) mark key lineage-specific genes. A new study now reports the identification of Mll2 (KMT2b) as the enzyme responsible for implementing H3K4me3 on bivalently marked promoters in ESCs.

Measuring gene expression in individual cells is crucial for understanding the gene regulatory network controlling human embryonic development. Single-cell RNA sequencing (RNA-Seq) analysis of 124 individual cells from human preimplantation embryos and embryonic stem cells (hESCs) now provides a comprehensive framework of the transcriptome landscapes of human early embryos and hESCs.

The crystal structure of the full catalytic core of p300 reveals the presence an unexpected RING domain, within the CH2 region, that folds over the HAT-domain substrate-binding pocket. Mutations that destabilize the RING-HAT interaction and increase acetyltransferase activity in vitro are also found in B-cell lymphomas, thus suggesting an important function for this autoinhibitory interaction in vivo.

How plant pri-miRNAs with complex secondary structures are recognized and processed has been unclear. A new study now suggests that unlike canonical processing of pri-miRNAs, terminal loop–branched pri-miRNAs can be processed by Dicer-like 1 (DCL1) complexes bidirectionally, either from the lower stem to the terminal loop or vice versa, resulting in productive and abortive processing of miRNAs, respectively.

Mitochondria contain multisubunit translocases to import preproteins from the cytosol. The presequence translocase of the inner membrane operates in a voltage-gated manner, but how a preprotein-conducting channel responds to the membrane potential was unknown. A new study identifies a voltage-coupled conformational change in a transmembrane segment of the Tim23 import channel, representing a major step toward understanding the molecular basis of a voltage-gated protein translocase.

The binding of stromal interaction molecule 1 (STIM1) to ORAI calcium channels is critical for store-operated calcium entry (SOCE), a calcium influx pathway conserved among nearly all vertebrate cells. Although many major steps of this pathway are well understood, crucial details regarding the mechanism of STIM1 activation remain unclear. A study in this issue provides important new insights into the conformational changes that occur during STIM1 activation.

The detailed mechanism by which the molecular motors kinesin and myosin travel along their respective protein tracks as they generate force during motile processes is still poorly understood. In a recent breakthrough, a crystal structure of kinesin in complex with tubulin illuminates the atomic-level details of a motor-track interaction, answering many questions yet leaving a number of mysteries unresolved.

Proteins containing repeats of the WASP homology 2 (WH2) actin-binding module are multifunctional regulators of actin nucleation and assembly. Now biochemical analyses of VopF from Vibrio cholerae reveal a new regulatory mechanism of actin-filament barbed-end dynamics including enhanced nucleation, uncapping and assisted elongation.

Elongation factor G (EF-G) facilitates the movement of tRNA and mRNA by one codon, which is coupled to the ratchet-like rotation of the ribosome complex and is triggered by EF-G–mediated GTP hydrolysis. The crystal structure of pretranslocational ribosome bound to EF-G trapped with a GTP analog provides insight into how the ribosome and EF-G are coordinated to modulate the GTPase activity.

N-terminal acetylases catalyze the cotranslational modification of myriad proteins. Structural and mutational analyses of the NatA complex, comprising a catalytic and auxiliary subunit, and of the catalytic subunit alone reveal the molecular basis for substrate binding, specificity and mode of catalysis, and the role of the auxiliary subunit in these activities.