Focus |

Genomes and Epigenomes

Rebecca Furlong: human genetics and evolutionary genomics. 

Anne Mirabella: genome instability, DNA repair and replication.

Carolina Perdigoto: chromatin, epigenetics and transcription.

Katie Ridd: cancer genomics and cancer epigenomics.

Welcome to the Nature Communications Editors’ Highlights webpage on genomes and epigenomes. Each month our editors select a small number of Articles recently published in Nature Communications that they believe are particularly interesting or important.

The aim is to provide a snapshot of some of the most exciting work published in the area of genomes and epigenomes at Nature Communications.

Make sure to check the Editors' Highlights page each month for new featured articles.

Rebecca Furlong

Mendelian randomization is a useful tool to infer causal relationships between traits, but can be confounded by the presence of pleiotropy. Here, the authors have developed MR-link, a Mendelian randomization method which accounts for unobserved pleiotropy and linkage disequilibrium between instrumental variables.

Article | Open Access | | Nature Communications

How Indigenous populations in the southern tip of South America have changed over time has been unclear. Here the authors generate genome-wide data for 20 ancient individuals and examine how past migrations and admixture events correlate to geography and shifts in the archaeological record.

Article | Open Access | | Nature Communications

Structural variants (SVs) contribute to the genetic architecture of many brain-related disorders. Here, the authors integrate SV calls from genome sequencing (n = 755) with RNA-seq data (n = 629) from post-mortem dorsal lateral prefrontal cortex to annotate the gene regulatory effects of SVs in the human brain and their potential to contribute to disease.

Article | Open Access | | Nature Communications

Horseshoe crabs have been morphologically stable across evolutionary time. Here, the authors generate a chromosome-level assembly for the mangrove horseshoe crab, with implications for innate immunity, and challenging assumptions about the role of genome duplication in adaptive radiation.

Article | Open Access | | Nature Communications

European populations underwent strong genetic changes during the Neolithic. Here, Furtwängler et al. provide ancient nuclear and mitochondrial genomic data from the region of Switzerland during the end of the Neolithic and the Early Bronze Age that reveal a complex genetic turnover during the arrival of steppe ancestry.

Article | Open Access | | Nature Communications

Membranous nephropathy (MN) is a rare autoimmune disease of podocyte-directed antibodies, such as anti-phospholipase A2 receptor. Here, the authors report a genome-wide association study for MN and identify two previously unreported loci encompassing the NFKB1 and IRF4 genes and additional ancestry-specific effects.

Article | Open Access | | Nature Communications

Vitamin D is a precursor of the steroid hormone 1,25-dihydroxyvitamin D3, and its deficiency is associated with many adverse health outcomes. Here, Revez et al. perform a genome-wide association study for circulating 25-hydroxyvitamin D in 417,580 individuals and test for potential causal relationships with other traits using Mendelian randomization.

Article | Open Access | | Nature Communications

Prior to genome assembly, the raw sequencing reads must be analyzed for assessment of major genome characteristics such as genome size, heterozygosity, and repetitiveness. For this purpose, the authors introduce GenomeScope 2.0, an extension of GenomeScope for polyploid genomes, and Smudgeplot, which can estimate a genome’s ploidy.

Article | Open Access | | Nature Communications

Anne Mirabella

The origin recognition complex (ORC) is essential for loading the Mcm2–7 replicative helicase onto DNA during DNA replication initiation. Here, the authors describe several cryo-electron microscopy structures of Drosophila ORC bound to DNA and its cofactor Cdc6 and also report an in vitro reconstitution system for Drosophila Mcm2–7 loading, revealing unexpected features of ORC’s DNA binding and remodeling mechanism during Mcm2–7 loading.

Article | Open Access | | Nature Communications

DNA damage sensors DDB2 and XPC are fundamental factors to initiate global genome nucleotide excision repair and protect DNA from mutagenesis. Here the authors reveal that ubiquitin and TFIIH-stimulated DDB2 dissociation promotes DNA damage handover to XPC in nucleotide excision repair.

Article | Open Access | | Nature Communications

While R-loops can alter cell homeostasis, it is unclear what determines their toxicity. Here, the authors, by using Top1 knockdown as a tool to enhance the formation of R-loops at certain genomic sites, reveal and characterize a proportion of R-loops that are more toxic to the cell by causing DNA damage.

Article | Open Access | | Nature Communications

In mammalian cells, during transcription and replication, RNA:DNA hybrid structures known as R-loops can arise, posing as obstacles to replication fork progression. Here the authors reveal that the ATP-dependent chromatin remodelling INO80 complex promotes resolution of R-loops to prevent replication associated DNA damage in cancer cells.

Article | Open Access | | Nature Communications

In order to avoid transcription-replication conflicts (TRCs) on shared DNA templates, cell must maintain strict spatiotemporal co-ordination of transcription with replication. Here the authors uncover a role for BRD4 in preventing TRCs and DNA damage checkpoint signaling in oncogenic cells.

Article | Open Access | | Nature Communications

Bacterial chromosomes are tightly packed, limiting structural analysis by imaging techniques. Here, by quantitative time-lapse single-cell imaging of widened Escherichia coli cells, Wu and Japaridze et al. show that the chromosome exhibits a ring-like torus topology and a dynamic domain structure.

Article | Open Access | | Nature Communications

Carolina Perdigoto

Chromatin state underlies cellular function, and transcription factor binding patterns along with epigenetic marks define chromatin state. Here the authors show that the histone chaperone ANP32E functions through regulation of H2A.Z to restrict genome-wide chromatin accessibility and to inhibit gene transcriptional activation.

Article | Open Access | | Nature Communications

Nucleosome turnover concomitant with incorporation of the histone variant H3.3 is a hallmark of regulatory regions in the animal genome. Here, the authors demonstrate that fast histone turnover and H3.3 incorporation defines a dynamic heterochromatin state in pluripotent stem cells.

Article | Open Access | | Nature Communications

Neuronal differentiation requires rearrangement of the transcriptional and chromatin landscapes of neural cells. Here, the authors study in-vitro neuronal differentiation of murine embryonic stem cells (ESCs) to show that this process is modulated by DOT1L activity, which regulates H3K79me2 accumulation, and preserves accessibility of SOX2-bound enhancers.

Article | Open Access | | Nature Communications

Allele-specific measurements can reveal differences in DNA methylation between homologous alleles associated with changes in genetic sequence. Here, the authors develop a method for detecting allele specific methylation events within haplotypes of linked SNPs, compare it with existing methods, and show it identifies haplotypes for which the genetic variant carries significant information about the methylation state of the allele of origin.

Article | Open Access | | Nature Communications

Polycomb (PcG) and Trithorax (TrxG) group regulate several hundred target genes with important roles in development and disease. Here the authors combine experiment and theory to provide evidence that the Polycomb/Trithorax system has the potential for a rich repertoire of regulatory modes beyond simple epigenetic memory.

Article | Open Access | | Nature Communications

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions with repetitive and restrictive behaviours. Here the authors integrate mRNA expression, miRNA expression, DNA methylation, and histone acetylation datasets from a collection of post mortem brain tissues and identify a convergent molecular subtype of ASD.

Article | Open Access | | Nature Communications

Tibetan adaptation to the high-altitude environment represents a case of natural selection during recent human evolution. Here the authors investigated the chromatin and transcriptional landscape of umbilical endothelial cells from Tibetan and Han Chinese donors and provide genome-wide characterization of the hypoxia regulatory network associated high-altitude adaptation.

Article | Open Access | | Nature Communications

TET mediated RNA-hydroxymethylation (5hmC) has been detected in mammals, but its physiological role remains unclear. Here the authors map 5hmC during embryonic stem cell (ESC) differentiation and find that Tet-mediated RNA hydroxymethylation reduces the stability of crucial pluripotency related transcripts.

Article | Open Access | | Nature Communications

Preimplantation embryos undergo extensive transcriptomic and epigenomic remodeling. Here the authors assay open chromatin in bovine oocytes, embryos, and embryonic stem cells, and compare the transcriptomes and epigenomes of cattle, human and mouse embryos, revealing species-specific regulation of genome activation.

Article | Open Access | | Nature Communications

Epigenetic mechanisms have emerged as contributors to the molecular impairments caused by exposure to environmental factors such as abused substances. Here the authors perform epigenetic profiling of the striatum and identify the tyrosine kinase FYN is an important driver of neurodegenerative-like pathology and drug-taking behaviour.

Article | Open Access | | Nature Communications

Katie Ridd

The evolutionary progression from primary to metastatic prostate cancer is largely uncharted, and the implications for liquid biopsy are unexplored. Here, the authors use deep genomic sequencing and histopathological information to trace tumor evolution both within the prostate and during metastasis in ten men.

Article | Open Access | | Nature Communications

There are currently only a few biomarkers to predict the response of muscle invasive bladder cancer to therapy. Here, the authors analyse 300 tumors using exome and RNA sequencing and find that tumors with a high degree of genomic instability and a non-basal/squamous gene expression subtype are most likely to respond to treatment.

Article | Open Access | | Nature Communications

Pancreatic ductal adenocarcinoma may be initiated by acinar metaplasia, but the molecular and cellular insights during this transition are unclear. Here the authors show, using single cell RNA-sequencing analyses, that mouse metaplastic acinar cells can be clustered into six cell types or states that are heterogeneous and have unique transcription programs.

Article | Open Access | | Nature Communications

Schizophrenia has been associated with increased risk of breast cancer, yet the risk of schizophrenia following breast cancer is unclear. Here, the authors show a bidirectional association between breast cancer and schizophrenia in Sweden and a shared genetic contribution to both diseases.

Article | Open Access | | Nature Communications

Mongolia has the highest incidence of—and mortality from—hepatocellular carcinoma (HCC) in the world. Here, the authors examine the genomic and transcriptomic landscape of Mongolian HCC, uncover novel driver mutations, and suggest distinct disease etiologies.

Article | Open Access | | Nature Communications

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Article | Open Access | | Nature Communications

Here the authors show that stronger immune selection and immune editing in females and younger patients lead to the accumulation of poorly presented driver mutations in tumors. These results may explain why young and female patients are characterized by lower response rates to immune checkpoint blockade therapies.

Article | Open Access | | Nature Communications

Genetic variants on chromosome 8q24 are associated with prostate cancer risk in men of African ancestry. Here the authors show that one of these variants, rs72725854 alters the enhancer activity in its region, which upon androgen stimulation, activates multiple oncogenic lncRNAs and c-myc.

Article | Open Access | | Nature Communications