Volume 52 Issue 9, September 2020

Binding of RNA to the gene expression regulator Polycomb repressive complex 2 (PRC2) has been proposed to antagonize PRC2’s chromatin recruitment. A new study now shows that RNA is in fact critical for correct recruitment of PRC2 at its target genes in human pluripotent stem cells and suggests that interplay of PRC2 and RNA can fine-tune PRC2’s regulatory role.

The role of N⁶-methyladenosine (m⁶A) is still not fully understood. Two new studies advance understanding of this RNA modification. One shows that m⁶A modification of nascent messenger RNA promotes transcription by recruiting the histone H3 K9 demethylase KDM3B. Another study identifies genetic variants that affect m⁶A deposition and human disease.

METTL3-induced deposition of N⁶-methyladenosine (m⁶A) in RNA correlates with removal of H3K9me2 genome wide. The m⁶A reader YTHDC1 recruits the H3K9me2 demethylase KDM3B to chromatin.

Quantitative ChIP–seq analysis maps G-quadruplex (G4) DNA structures in breast cancer patient-derived tumor xenograft (PDTX) models. G4-based subtypes highlight additional tumor heterogeneity in the integrative cluster (IC) system.

Nucleic acid processing by the cytoplasmic exonuclease TREX1 and cytosine editing by APOBEC3B drive chromothripsis and kataegis during telomere crisis.

A pan-cancer analysis finds that extrachromosomal DNA is pervasive and associated with oncogene amplification and poor patient outcomes.

MOBSTER is an approach for subclonal reconstruction of tumors from cancer genomics data on the basis of models that combine machine learning with evolutionary theory, thus leading to more accurate evolutionary histories of tumors.

Single-cell RNA-seq and in vivo lineage tracing identify unique luminal progenitors in the mouse prostate that can contribute to regeneration and oncogenesis. Single-cell RNA-seq analysis of human prostate identifies a similar cell population.

Genome-wide analysis of 3D chromatin topologies across gastric cancers suggests that Epstein–Barr virus infection may induce the epigenetic rewiring of EBV-positive tumors through human–viral chromatin interactions, a phenomenon termed ‘enhancer infestation’.

Perturbation of RNA–PRC2 interaction in human pluripotent stem cells disrupts PRC2 chromatin occupancy and localization genome wide. PRC2–RNA interactions contribute to cardiomyocyte differentiation.

Quantitative trait locus (QTL) mapping of N⁶-methyladenosine (m⁶A) in human cells highlights the role of RNA-binding proteins, RNA secondary structure and context-dependent m⁶A effects. m⁶A QTLs are enriched in loci associated with immune and blood-related traits.

De novo genome assemblies of four European flint maize lines and comparison with two US Corn Belt genomes provide insights into the dynamics of intraspecies variation in repeat and gene content in maize genomes.

A new statistical framework to classify mutagenesis clusters identifies a novel, diffuse hypermutation pattern, named omikli, that is induced by APOBEC3 and associated with mismatch-repair activity.

STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.