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Histones are recognized by epigenetic readers, which play essential roles in regulation of chromatin and transcription. Here the authors provide evidence that the ZZ-type zinc finger domain of ZZZ3 functions as a reader of histone H3, which is required for the ATAC complex-mediated maintenance of histone acetylation and gene activation.

Zinc finger design is facilitated with a deep-learning model.

Neutrophils are increased in response to injury and infection but how they form from a common granulocyte-macrophage progenitor is unclear. Here, the authors identify a role for the transcriptional repressor ZBTB11 in zebrafish, which is regulated by master myeloid regulators and repressesTP53.

Strikoudis et al. show that Phf5a is necessary for ESC self-renewal, efficient iPSC reprogramming and contributes to muscle specification by stabilizing Paf1C and controlling RNA polymerase II elongation.

An in vitro method for examining cleavage patterns of zinc-finger nucleases (ZFNs) identifies previously unknown off-target cleavage sites. Some of the sites are present in the human genome and show evidence for ZFN-induced cleavage in cultured human cell lines.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Context-dependent assembly (CoDA) of zinc finger nucleases is reported. Starting from an archive of zinc finger modules known to function well together, effective multifinger arrays can be constructed using standard techniques. Also in this issue, Doyon et al. report rational design of nucleases with improved cleavage activity.

An efficient method for gene targeting in plants has been lacking until now, frustrating efforts to engineer crop plants. Here it is demonstrated that zinc-finger nucleases—enzymes engineered to create DNA double-strand breaks at specific loci—can be used for gene targeting, in this case inducing mutations that confer resistance to herbicides in tobacco plants.

A chromosomal translocation found in certain acute myeloid leukaemia (AML) patients results in fusion of the plant homeodomain (PHD) finger of a chromatin-binding protein to a common fusion partner, nucleoporin-98 (NUP98). By binding chromatin, the NUP98–PHD fusion protein—found to be a potent oncoprotein that induces AML—apparently locks developmentally important genes into an active state.

Lung adenocarcinomas bearing the ID2 mutational signature display increased LINE-1 retrotransposon activity, which contributes to their fast evolutionary dynamics and aggressive phenotype.

RAG2, a component of the V(D)J recombinase, has a plant homeodomain (PHD) domain which specifically recognizes histone H3 trimethylated at lysine 4 (H3K4me3). A crystal structure of the complex is presented, and the interaction between RAG2 and H3K4me3 shown to be important for V(D)J recombination in vivo.

Genetic engineering in plants remains laborious and time consuming, with no precise genetic engineering methods comparable to those available in animal models. A new approach that relies on the use of designed zinc-finger nucleases is showcased here in maize, inducing herbicide tolerance that is stably inherited.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

Commercially available bionic hands can replicate many movements, but controlling a multiarticulate bionic hand is not an intuitive task. Here, the authors describe the integration of proximity and pressure sensors into a commercial prosthesis to enable autonomous grasping

A chemical mutagenesis screen identifies RNF121 as an oncogenic cofactor for MYCN in neuroblastoma.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

A genome-wide association study meta-analysis combined with multiomics data of osteoarthritis identifies 700 effector genes as well as biological processes with a convergent involvement of multiple effector genes; 10% of these genes express the target of approved drugs.

Variable New Antigens Receptors (VNARs) from shark antibodies possess a unique molecular dexterity that allows them to access epitopes inaccessible to conventional antibodies. Here, the authors use crystallography to investigate how two VNARs selectively engage soluble TNF-alpha.

This study demonstrates the capability of deep learning protein design models in generating functionally validated β-strand pairing interfaces, expanding the structural diversity of de novo binding proteins and accessible target surfaces.

An analysis of the localization and intensity of intracortical microstimulation in three participants with cervical spinal cord injury shows that overlapping projected fields from multiple electrodes produce sensations that are more easily localizable.

Mutations of the histone H3K36-specific methyltransferase ASH1L have been linked to several human diseases. Here, the authors report the mechanism by which three C-terminal domains in ASH1L regulate its enzymatic activity and interact with chromatin.

Stem cell repair of injured monkey spinal cords restores hand function in 53% of trials.

Genetic variants at multiple loci of chr5p15.33 have been associated with susceptibility to numerous cancers. Here the authors show that the association of one of these loci may be explained by a variant, rs36115365, influencing telomerase reverse transcriptase (TERT) expression via ZNF148.

G protein-coupled receptor di/oligomers can diversify signaling and play roles in disease. Here authors stabilized D2 dopamine receptor di/oligomers that may selectively favor complexes with the adaptor protein β-arrestin2 to bias receptor activity.

Cheng et al., use non-infectious stable viral replicon cell lines in genome-wide CRISPR KO screens across diverse viral pathogens to identify host factors specifically involved in the intracellular stages of viral replication.

BPTF is known to regulate chromatin accessibility and self-renewal in mammary epithelial stem cells. Here, the authors discover that BPTF inhibition delays tumor formation, re-activates ERα expression, increases sensitivity to tamoxifen treatment, and inhibits metastatic development.

Following spinal cord injury, gamified physical therapy that incorporates closed-loop vagus nerve stimulation can aid restoration of arm and hand function.

Here the authors record the responses evoked in the hand and arm representations of M1 during intracortical microstimulation in the hand representation of S1, and show somatotopically organized connections with motor cortex. The resulting interference with motor decoding is task dependent but can be alleviated by using biomimetic stimulation.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

Deep learning methods have been used to design proteins that can neutralize the effects of three-finger toxins found in snake venom, which could lead to the development of safer and more accessible antivenom treatments.

A study using high-density surface recordings of the speech cortex in a person with limb and vocal paralysis demonstrates real-time decoding of brain activity into text, speech sounds and orofacial movements.

The signaling adaptor TRAF6 is a ubiquitin E3 ligase whose activity can lead to activation of NF-κB and MAPK pathways. New data based on the structure of TRAF6 in complex with the ubiquitin E2 Ubc13 suggest that other TRAFs do not interact with Ubc13 and that oligomerization of TRAF6 is needed for downstream signal transduction.

A purpose-built implantable system based on biomimetic epidural electrical stimulation of the spinal cord reduces the severity of hypotensive complications in people with spinal cord injury and improves quality of life.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

Analysis of medulloblastomas in humans and mice shows that the functional consequences of ZIC1 mutations are exquisitely dependent on the cells of origin that give rise to different subgroups of medulloblastoma.

Giant viruses are large DNA viruses with capsid diameters up to 500 nm. Given technical challenges only few high-resolution structures of viral capsids exist. Here, Shao et al. provide a nearatomic structure of giant virus PBCV-1 capsid and resolve the previously unknown asymmetric capsid components. The local capsid microenvironments created by these components provide insights into the mechanism of capsid assembly of giant viruses.

Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index. Gene-based meta-analysis and functional studies implicate 13 genes, eight of which are novel, and neuronal pathways as factors in human obesity.

Epithelial cells that line the gut secrete complex glycoproteins that form a mucus layer to protect the gut wall from enteric pathogens. Here, the authors provide a comprehensive characterisation of endo-acting glycoside hydrolases expressed by mucin-degrading members of the microbiome that are able to cleave the O-glycan chains of a range of different animal and human mucins.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

A minimal artificial Kitaev chain can be realized by using two spin-polarized quantum dots in an InSb nanowire strongly coupled by both elastic co-tunnelling and crossed Andreev reflection.