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Ahmad et al. show that soluble histone H4 binds at histone genes and acts as a repressor of their expression. These findings suggest that histone H4 is a sensor of ongoing DNA replication. Ongoing chromatin assembly uses up soluble H4 and relieves histone gene repression; however, once DNA replication ceases, soluble H4 accumulates and represses the histone genes.

Understanding gene regulation will require mapping specific chromain features in a small number of cells at high resolution. Here the authors describe CUT&Tag, which uses antibody-mediated tethering of Tn5 transposase to a chromatin protein to generate high resolution libraries.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

Conducting epigenomic studies on FFPE samples is traditionally challenging due to chromatin damage caused due to exposure to formaldehyde. Here, the authors show that an optimisation of their previous CUTAC method allows the production of high-resolution maps of regulatory elements from FFPE samples.

An improved method for single-cell analysis of histone modifications is applied to stem cell differentiation and cancer.

The effects of chromosomal translocations involving the mixed-lineage leukemia (MLL) locus on gene expression regulation remain to be explored. Here, the authors find that MLL oncoproteins support lineage-switching events through dynamic chromatin binding.

A scalable barcoding method measures multiple chromatin-associated proteins in single cells.

Automated and single-cell CUT&Tag is used to characterize the effects of KMT2A fusion proteins on chromatin in human primary leukemia samples, identifying oncogenic networks and fusion-specific therapeutic vulnerabilities.

Centromeric DNA repeats can be thought of as selfish elements that constantly compete to beat the odds and make it into the egg at meiosis.

This work presents RT&Tag, which captures RNA molecules in proximity to a protein of interest in intact nuclei.

A chemical-genetic approach coupled with temporally resolved chromatin profiling shows that RNAPII promoter-proximal pausing stabilizes BAF complex occupancy and promotes nucleosome eviction.

A 3D model of human segmentation and somitogenesis derived from induced pluripotent stem cells captures the oscillatory dynamics of the segmentation clock as well as morphological and molecular features of the developing embryonic axis and tail.

The authors describe a streamlined epigenomic profiling protocol based on cut-and-paste tagmentation by the Tn5 transposase targeted to a chromatin protein of interest.

GLI repression has been presumed to be the default transcriptional state and important for pre-patterning tissues. Challenging current models, the authors show that GLI3 repression is inert in the limb bud before the onset of Hedgehog signaling.

A method to map transcription factor binding across the genome, at high resolution and without cross-linking.

Short H2A variants are testis-specific histones that destabilize nucleosomes during spermatogenesis. In this study, the authors show that these variants are expressed in an array of different cancers and identify splicing changes associated with nucleosome instability in these malignancies.

Several models have been proposed to explain the spreading of heterochromatin, including looping, sliding and oozing. A review of studies from diverse model eukaryotes allows the authors to evaluate the existing models and leads them to propose a common, ancestral mechanism for spreading.

This protocol describes CUT&RUN, a genome-wide targeted epigenetic profiling method that allows the analysis of low cell numbers at high resolution.

The development of new strategies to deplete maternal histone proteins in vivo and in vitro has led to the discovery of unexpected roles of histones in forming a functional nuclear envelope.

The much-anticipated publication of the ENCODE pilot project, representing a detailed and comprehensive characterization of 1% of the human genome, has demonstrated how little we truly understand about how our genes are regulated. Transcripts are nearly everywhere, regulatory sequences remain poorly defined and evolutionary conservation is a surprisingly inadequate predictor of transcriptional features.

Fusions of Cas9 to histone-modifying enzymes enable functional interrogation of the epigenome.

In chromatin endogenous cleavage (ChEC), micrococcal nuclease (MNase) is fused to a protein of interest and its cleavage is thus targeted to specific genomic loci in vivo. Here, the authors show that time-resolved ChEC-seq (high-throughput sequencing after ChEC) can detect DNA shape patterns regardless of motif strength.

The resolution of epigenomic profiling has been vastly augmented with the adoption of new approaches to interrogate varied features of the epigenome. This Review describes these techniques and outlines the ways in which these genome-wide tools can be used to examine the epigenome.

This protocol provides guidelines for performing single-cell combinatorial indexing cleavage under targets and tagmentation. This method builds on the existing cleavage under targets and tagmentation method and uses a combinatorial indexing step to allow single-cell profiling of chromatin modifications.

Chromatin marks, including histone modifications and variants, have become important tools for characterizing epigenomes, yet how they might interact with one another to facilitate gene expression and regulation has remained unclear. A new study maps unstable nucleosomes containing both H3.3 and H2A.Z histone variants to human promoters and regulatory elements and suggests that transient occupancy by double-variant nucleosomes is a general feature of eukaryotic gene regulation.

When environmental temperatures rise, plants seek help from their core molecular mechanisms to adapt. The chromatin protein H2A.Z, which regulates gene expression, is one such rescue molecule.

To test the effect of transcription-generated torsional stress on nucleosome dynamics and RNA polymerase II (Pol II) kinetics in Drosophila cells, a new study reports a genome-wide sequencing-based assay to measure torsional states at the gene level. Inhibition of topoisomerases leads to rapid accumulation of torsional strain accompanied by changes in Pol II kinetics and destabilization of nucleosomes.

Histone core particles are spools for wrapping DNA, whereas histone variants have evolved diverse additional roles in chromosome metabolism. Some variants mediate universal functions, such as chromosome segregation and DNA repair, and others specialize in organism-specific tasks.

Nucleosomes consist of two copies of each histone. H2A.Z is a variant H2A-related histone known to be enriched around transcription start sites. However, an H2A.Z-containing nucleosome could contain contain two copies of H2A.Z (homotypic) or one of H2A.Z and one of canonical H2A (heterotypic). Homotypic and heterotypic H2A.Z nucleosomes are now mapped and their distributions relative to promoters analyzed.

Eukaryotes differ substantially from bacteria and archaea owing to their nucleosome-based packaging of DNA. In this Review, Talbert, Meers and Henikoff place gene regulation in an evolutionary context by discussing how the emergence and diversification of eukaryotic chromatin provided both challenges and opportunities for intricate mechanisms of gene regulation in eukaryotes.

In most cancers, mutations that lead to oncogene activation and tumor suppressor inactivation synergize to promote tumorigenesis. However, in neuroblastomas, MYCN amplification and ATRX mutations are mutually exclusive and incompatible.

This is an issue edsumm for ng1929. Identification of the Palaeocene/Eocene thermal maximum in a marine sedimentary sequence. It shows that sea surface temperatures near the North Pole increased from roughly 18 degrees Celsius to over 23 degrees Celsius — such warm values imply the absence of ice and thus exclude the influence of ice-albedo feedbacks on this Arctic warming.