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Here, the authors show that bromodomain-containing protein 4 is recruited to the MYC enhancer by Mediator and activates transcription through elongation factors independently of bromodomains. This mechanism contributes to bromodomain and extraterminal domain inhibitor resistance in estrogen receptor-positive breast cancer.

Exocytosis of secretory vesicles is required for cellular growth, cellular division and cell–cell communication. Lee et al. reveal that the exocyst tethering complex has stimulatory roles in exocytic soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly and SNARE-mediated vesicle fusion.

Using cryo-electron tomography of human T cell leukemia virus type 1 virus-like particles, the authors reveal that the immature Gag lattice is stabilized by the capsid N-terminal domain in contrast to other retroviruses that use the C-terminal domain.

Germline small RNAs in plants and mammals are marked by pseudouridine. In plants, Exportin-t is required for pseudouridylation, transport and localization of small RNAs in pollen, as well as for epigenetic inheritance in the form the triploid block.

Anti-NMDA receptor encephalitis is the most common autoimmune encephalitis. Michalski et al. reveal epitope diversity, conformational changes and functional impacts of the autoantibodies using cryo-EM and electrophysiology.

Here, using mouse genetics, biochemistry and cell-based experiments, the authors reveal that shieldin primarily catalyzes DNA priming and polymerase-dependent fill-in synthesis at 5′ recessed DNA ends during the joining of activation-induced cytidine deaminase-dependent DNA breaks.

The authors cloned anti-NMDAR (N-methyl-d-aspartate receptor) monoclonal antibodies from the immune B cells of persons with autoimmune encephalitis and revealed their precise binding epitopes on NMDARs and the pathological mechanism underlying the downregulation of synaptic function.

This work reveals structures of biotin-dependent carboxylases in different states, provides notable insight into their catalytic mechanism and may help the development of new drugs for the treatment of related diseases.

Methyl-CpG-binding protein 2 (MeCP2) is a master regulator of neuronal gene expression, and its genetic mutations cause the neurodevelopmental disorder Rett syndrome. Single-molecule experiments have enabled the direct visualization of the dynamics of MeCP2 on DNA, shedding light on how the specific chromatin context tunes MeCP2 function.

The study presents cryo-electron microscopy structures of human autophagy-related protein (ATG) 2A in complex with WD-repeat protein interacting with phosphoinositides 4 (WIPI4) and the ATG2A–WIPI4–ATG9A complex, providing insights into spatially coupled lipid transport and re-equilibration during autophagosome formation.

Two recent studies provide mechanistic insights into how LIN28A controls changes in cell fate identity, focusing on either a let-7-independent or let-7-dependent pathway of action involving LIN28A.

Using single-molecule techniques, the authors find that the methyl-CpG-binding protein MeCP2, whose mutations cause Rett syndrome, exhibits distinctive behaviors when bound to nucleosomes versus free DNA, thus directing its multifaceted functions on chromatin.

Here, the authors develop an assay to measure DNA supercoiling, revealing DNA supercoiling domains across the human genome that are modulated by topoisomerase and showing their colocalization with nuclear compartments and impact on gene expression.

Combining genome engineering, epigenomics and multiplex three-dimensional microscopy approaches, the authors show that PRE chromatin loops form a topological scaffold, restricting promoter–enhancer communication and contributing to enhancer–promoter specificity.

Using cryo-EM, the authors revealed structures of ESCRT-III superfamily member PspA and the molecular basis of structural plasticity that enables assembly modulations by the addition of nucleotides and targeted mutations.

The extracellular AMPA receptor N-terminal domain (NTD) affects synaptic strength by tuning receptor diffusion. We reveal that pH fluctuations accompanying synaptic activity alter NTD conformation of the functionally dominant GluA2 subunit, via proton sensing by an NTD histidine residue, thereby increasing gating kinetics and receptor diffusion at the synapse.

Combining patch-clamp electrophysiology, molecular dynamics simulations, cryo-electron microscopy and imaging of neuronal synapses, the authors reveal how AMPA glutamate receptors are regulated by protons that are released from synaptic vesicles during signal transmission.

Here, using cryo-electron microscopy to study the structure of LRPPRC (leucine-rich pentatricopeptide repeat-containing protein) in complex with SLIRP (SRA stem-loop-interacting RNA-binding protein), mRNA and the mitoribosome, the authors show that LRPPRC facilitates mRNA handoff to the mitoribosome and regulates the expression of several mitochondrial genes.

Here, the authors examine and discuss the functional complexity and cellular implications of X–Y pairs, homologous genes expressed in the human sex chromosomes.