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A technique called condense-seq has been developed to measure nucleosome condensability and used to show that mononucleosomes contain sufficient information to condense into large-scale compartments without requiring any external factors.

A synthetic biology system called SMART has been developed that uses conditional protein splicing for the programmable ligation of functional proteins from previously defined molecular combinations on cell surfaces.

A method for engineering chemically modified proteins has now been developed using a chemoenzymatic cascade of sortase-mediated transpeptidation and protein trans-splicing. Using this one-pot approach enabled the generation of site-specifically modified proteins in vitro and in isolated cell nuclei.

A high-throughput approach using a DNA-barcoded nucleosome library shows that ISWI chromatin remodellers can distinguish between differently modified nucleosomes.

Ubiquitylation of H2B is associated with transcription and regulation of chromatin structure. Here, the authors perform an unbiased screen to identify the role of chromatin modifications on ubiquitylation of H2BK120 and characterize the crosstalk between H2BK120ub and H2A modifications and variants.

Time-resolved synthesis of target proteins via proximity-triggered protein trans-splicing has now been shown to enable the activation of a diverse set of proteins upon the addition or removal of control elements. This temporal precision allows for monitoring distinct phases in cellular signaling and unveiling the molecular connections of oncofusion kinases, including DNAJ–PKAc.

Combined use of a DNA-barcoded nucleosome library and a humanized yeast library allows the identification of histone globular domain mutations that affect histone exchange and nucleosome sliding processes, as well as cancer-associated gene pathways.

A proximity labelling-based approach for mapping nuclear protein–protein interactions is described that could advance epigenetic drug discovery.

TG2 functions as an eraser and exchanger of H3 monoaminylations, including histaminylation of Gln5 of histone H3.

Proteins that interact with histone post-translational modifications have now been identified using an approach based on split-intein mediated histone semisynthesis. Histone modifications and disease-relevant mutations were installed into native chromatin with an adjacent photocross-linker to enable in situ cross-linking. This strategy enabled the determination of chromatin-relevant interactomes and represents a powerful tool for exploring epigenetic regulation and dysregulation at the molecular level.

Bisphosphoglycerate mutase (BPGM) drives phosphoglycerate mutase 1 (PGAM1) phosphorylation, which is required for glycolytic flux. Loss of BPGM is partially compensated by 1,3-BPG directly phosphorylating PGAM1, sustaining glycolytic flux but diverting metabolites for serine synthesis.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

A synthetic library of nucleosomes, each with a DNA-barcode characteristic for a defined post-translational modification (PTM), is used to probe PTM-based recruitment and modulation of histone mark readers and writers.

Studies of histidine phosphorylation have been limited owing to a lack of appropriate tools. The synthesis of a stable phosphohistidine mimic now leads to a pan antibody, enabling detection and further functional investigations of this little-known post-translational modification.

A method for engineering site-specific modifications of histone proteins within cellular chromatin has been developed using protein trans-splicing. This approach enabled a native histone modification, H2BK120 ubiquitination, to be incorporated in isolated nuclei, which was shown to trigger a downstream epigenetic effect.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

A photocrosslinking-based nucleosome profiling approach is used to identify a conserved basic motif in the ISWI remodeler SNF2h that anchors it to the acidic patch of nucleosome and enables nucleosome sliding activity.

Missense mutations in histones can drive oncogenesis and disrupt chromatin, but the associated mechanisms for many such mutations remain poorly understood. Here, the authors show that cancer-associated histone mutations at arginines in the H3 N-terminal tail disrupt repressive chromatin domains, alter gene expression, and in one case impair differentiation via reduction of PRC2 function.

PFA tumours express high levels of EZHIP (also known as CXORF67). Here the authors find that EZHIP directly interacts with the active site of EZH2 and is a competitive inhibitor of PRC2 and that EZHIP gives rise to H3K27me3 genomic profile similar to the K27M oncohistone.

A conjugate generated by expressed protein ligation between an antibody targeting dendritic cells (DCs) and an immune-stimulating double-stranded DNA reveals that DCs can mediate both innate and adaptive immunity and represents its potential utility as a vaccine adjuvant.

The ubiquitylation of histone H2B on lysine 120 is an important modification with roles in a diverse range of nuclear processes. Here, the authors use 'designer' chromatin to show that H2B-ub orients hDot1L into the correct position for activation.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

The histone-acetylation-reader protein ENL is mutated in a paediatric kidney cancer in such a way that it clusters at target genes, increasing the recruitment of the transcriptional machinery, enhancing transcription and deregulating cell fate during development.

In serotonin-rich tissues, tissue transglutaminase 2 is able to attach serotonin to a glutamine residue in histone H3; this modification mediates permissive gene expression in these tissues.

Semisynthetic methods to make ubiquitin conjugates have yielded broad conclusions for epigenetics. A robust intein-mediated chemical crosslinking strategy now expands our understanding by showing that a methyltransferase is surprisingly tolerant of changes to ubiquitin location and composition.

Polycomb group (PcG) proteins are transcriptional repressors that modify chromatin and regulate important developmental genes. One PcG-associated, chromatin-modifying activity is an enzyme that ubiquitinates histone H2A of chromatin. Here, a fruitfly PcG complex that is associated with H2A deubiquitination, and thereby with gene repression, is identified. PcG-mediated gene silencing might thus involve a dynamic balance between ubiquitination and deubiquitination of H2A.

Suv39h1 is a histone methyltransferase that methylates H3K9 residues in heterochromatic regions of the genome. An approach using semisynthetic chromatin reveals a mechanism for heterochromatin spreading in which H3K9 trimethylation anchors and activates Suv39h1 for modification of proximal lysines.

Ubiquitylated histone H2B (uH2B) is a known chromatin modification involved in transcription. Analysis of nucleosome arrays containing chemically synthesized uH2B proteins revealed that this posttranslational modification impairs chromatin fiber compaction and increases its accessibility through a mechanism distinct from other chromatin marks.

The chromosomal kinase JIL-1 is responsible for interphase histone H3S10 phosphorylation and has been proposed to protect active chromatin from heterochromatinisation. Here, the authors show that JIL-1 is stabilized and anchored to active genes and telomeric transposons by JASPer, which binds to H3K36me3 nucleosomes via its PWWP domain.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Roger Milne and colleagues conduct a genome-wide association study for estrogen receptor (ER)-negative breast cancer combined with BRCA1 mutation carriers in a large cohort. They identify ten new risk variants and find high genetic correlation between breast cancer risk for BRCA1 mutation carriers and risk of ER-negative breast cancer in the general population.

Hydrogen–deuterium (H/D) exchange combined with NMR spectroscopy analysis of nucleosomal arrays identified an acidic patch on ubiquitin that mediates chromatin decompaction and further supports that ubiquitin–ubiquitin interactions are needed for chromatin solubilization.

Intein splicing occurs in four steps, but the mechanisms controlling these steps — and thus preventing aberrant splicing — are unknown. Kinetic and NMR analysis of several complex constructs now identifies the rate limiting step as well as the conformational trigger that catalyzes this transformation.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

A combination of cell-based and biochemical approaches reveals how oncogenic fusion protein SS18-SSX directs BAF complexes to H2AK119Ub-modified nucleosomes to remodel chromatin at cancer-specific gene targets.

Various models have been proposed for control of autoinhibition of the signaling adaptor protein Crk-II. A thermodynamic, kinetic and structural analysis reveals a crucial role for selective domain destabilization in tuning the responsiveness of Crk-II to activation.

Covalent attachment of quorum-modulating peptides to surfaces can regulate Staphyloccocus aureus biofilm formation.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

The characterization of missense histone mutations that occur across several cancer types provides insight into the potential role of these mutations in altering chromatin structure and potentially contributing to tumour development.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

Active surveillance of men with prostate cancer has received increasing interest over the past decade, resulting in the publication of a wide range of different guidelines on the management of patients in active surveillance programmes, often with very different recommendations. Here, authors describe the various available guidelines and how they differ from each other, highlighting the need for an international consensus on the optimal use of active surveillance in patients with prostate cancer.

Biochemical reconstitution of PRC2 interactions with chromatinized templates demonstrates that protein-free linker DNA dominates the PRC2-nucleosome interaction, while RNA inhibits binding.

Determining progress in adaptation to climate change is challenging, yet critical as climate change impacts increase. A stocktake of the scientific literature on implemented adaptation now shows that adaptation is mostly fragmented and incremental, with evidence lacking for its impact on reducing risk.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.