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Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

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.

Jorge Ferrer, Jason Lieb, and Karen Mohlke and colleagues identify regulatory DNA active in human pancreatic islets by formaldehyde-assisted isolation of regulatory elements (FAIRE) coupled with high-throughput sequencing. They identified 80,000 open chromatin sites and 3,300 islet-selective open chromatin sites and found that a TCF7L2 intronic variant associated with type 2 diabetes is located in islet-selective open chromatin.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Brian Oliver, Jason Lieb, Christine Disteche and colleagues present an analysis of expression data in mammals, C. elegans and Drosophila. They conclude that dosage compensation corrects the imbalance in the number of X chromosomes relative to autosomes by upregulating X-linked genes in both males and females.

Jason Lieb and Sebastian Pott review the identification and composition of super-enhancers and ask whether super-enhancers are a new, conceptually distinct regulatory entity.

Understanding the pathology in the lungs of patients with COVID-19 might provide clues as to the susceptibility of patients and how the SARS-CoV-2 virus can be fatal. Here the authors analyze cadaveric pulmonary tissue and show one group with high viral load, early death, inflammation and inflammatory damage, and another with low viral load, longer duration of disease, and more M2-like polarization and fibrotic lung damage.

An extensive map of human DNase I hypersensitive sites, markers of regulatory DNA, in 125 diverse cell and tissue types is described; integration of this information with other ENCODE-generated data sets identifies new relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns.

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

Antibodies are a primary tool to assess histone post-translational modifications. However, different antibodies and batches might vary in their ability to recognize those modifications, depending on the kind of assay used. Now a systematic analysis of different antibodies and an open database containing the validation results are presented.

Myles Brown and colleagues analyze chromatin organization of androgen receptor-responsive transcriptional enhancers in a prostate cancer cell line. The authors develop a model to identify other genomic regions showing similar dynamic changes in chromatin structure, and identify other transcription factors that are involved in cellular responses to androgen.

The next step after sequencing a genome is to figure out how the cell actually uses it as an instruction manual. A large international consortium has examined 1% of the genome for what part is transcribed, where proteins are bound, what the chromatin structure looks like, and how the sequence compares to that of other organisms.

The spatial organization of cells in solid tumors is considered to be important for immune response and response to therapy. Here the authors use multiomics including spatial transcriptomics of human lung tumors prior to patients being treated and show among other things an association of stem-immunity hubs rich in stem-like CD8⁺ T cells with positive response to anti-PD-1 therapy.

The authors analyze how sequencing depth, choice of control sample, paired-end versus single-end reads and the selection of peak-calling algorithm influence the interpretation of chromatin immunoprecipitation–sequencing (ChIP-seq) experiments.

Eran Segal and colleagues report that promoters driving expression of cellular respiration genes in aerobic yeast species encode relatively open chromatin, whereas promoters associated with the same genes in anaerobic yeast species encode relatively closed chromatin. These results suggest that phenotypic diversity may in part be influenced by changes in the DNA-encoded nucleosome organization of promoters.

Automated pathotyping of synovial tissue in arthritis is a major unmet need. Here, the authors develop and demonstrate the efficacy of an automated tissue and cellular pathotyping tool for inflammatory arthritis.

When the two graphene sheets in a van der Waals heterostructure are twisted relative to each other by a specific amount, Mott-like insulating phases are observed at half-filling.

A large collection of new modENCODE and ENCODE genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human are analysed; this reveals many conserved features of chromatin organization among the three organisms, as well as notable differences in the composition and locations of repressive chromatin.

Competition ChIP with a sequence-specific S. cerevisiae transcription factor, Rap1, reveals that long Rap1 residence is coupled to transcriptional activation, whereas fast binding turnover is linked to low transcriptional output, suggesting that DNA-binding events that appear identical by conventional ChIP may have different underlying modes of interaction, leading to opposing functional outcomes.

NOTCH3 signalling is shown to be the underlying driver of the differentiation and expansion of a subset of synovial fibroblasts implicated in the pathogenesis of rheumatoid arthritis.

Centromere identity is thought to be epigenetically propagated by stable inheritance of nucleosomes containing the histone variant CENP-A; the authors propose a different model here in which germline transcription defines the genomic regions that exclude CENP-A incorporation during embryogenesis in the holocentric worm Caenorhabditis elegans.

This study tests the importance of the intrinsic DNA sequence preferences of nucleosomes by measuring the genome-wide occupancy of nucleosomes assembled on purified yeast genomic DNA. The resulting map is similar to in vivo nucleosome maps, indicating that the organization of nucleosomes in vivo is largely governed by the underlying genomic DNA sequence.

Despite the successes of genomics, little is known about how genetic information produces complex organisms. A look at the crucial functional elements of fly and worm genomes could change that.

New experimental approaches combined with statistical models show that DNA sequence strongly influences how the genome is packaged into nucleosomes. The studies predict that genes regulated by fundamentally different mechanisms have distinct nucleosome positioning signatures encoded in their DNA.

Transcription-coupled nucleosome turnover provides an opportunity to incorporate new nucleosomes at active genes. Swapping nucleosomes that contain silencing marks with those that are more permissive for transcription may provide a mechanism for remembering the activity state of a gene through the cell cycle.

Defining cell types and their activation status in rheumatoid arthritis (RA) is critical to understanding this disease. Raychaudhuri and colleagues leverage several single-cell -omics approaches to define the cellular processes and pathways in the human RA joint.

DNase-chip and DNase-array: similar names for two different new approaches that give a genomic perspective to the conventional DNase I hypersensitivity assay used to measure chromatin accessibility.

Our understanding of the molecular steps that occur during reprogramming somatic cells to induced pluripotent stem cells has recently been improved through analyses of cell populations and single cells. Here the authors consider the phases of reprogramming, models for describing the process and the roles of reprogramming factors.