Gene expression

  • Article
    | Open Access

    Here, authors present results of a hiPSC transcriptomics study on corticogenesis from multiple donors across four transitions in differentiation. They present a bulk data deconvolution method and show that co-culturing human NPCs with rodent astrocytes results in mutually synergistic maturation.

    • Emily E. Burke
    • , Joshua G. Chenoweth
    •  & Andrew E. Jaffe
  • Article
    | Open Access

    HER2-enriched breast cancers within the HER2-positive subtype are addicted to the HER2 pathway. Here, the authors analyse gene expression before, during, and after treatment with anti-HER2-based therapies in the phase II PAMELA clinical trial, finding phenotypic changes induced by treatment.

    • Fara Brasó-Maristany
    • , Gaia Griguolo
    •  & Aleix Prat
  • Article
    | Open Access

    For most human genes nearby regulatory variants explain only a small proportion of their expression variation between individuals. Here the authors show how the impact of a gene’s set of nearby regulatory variant is often linked to the expression levels of distal genes, providing insights into gene networks.

    • D. Wragg
    • , Q. Liu
    •  & J. G. D. Prendergast
  • Article
    | Open Access

    Gene expression and how genetic variants can influence gene expression are tissue-specific processes with important implications for phenotypes. Here, Richardson et al. use eQTL data from GTEx and the eQTLGen project in a two-sample SMR + HEIDI framework for causal inference of gene expression associations with complex trait.

    • Tom G. Richardson
    • , Gibran Hemani
    •  & George Davey Smith
  • Article
    | Open Access

    Quantification and characterization of circRNAs in sequencing data remains challenging, hindering efforts to understand their roles and regulation. The algorithm introduced here enables accurate circRNA quantification and permits insight into competitive splicing between linear and circular isoforms.

    • Jinyang Zhang
    • , Shuai Chen
    •  & Fangqing Zhao
  • Article
    | Open Access

    In C. elegans the chaperone hsp-16.2 predicts the penetrance of mutations and lifespan after heat shock, but it is not known why cells express different amounts of hsp-16.2. Here the authors show hsp-16.2 tracks differences in global gene expression capacity, rather than differences in signaling or intrinsic noise in adult intestine cells.

    • Nikolay Burnaevskiy
    • , Bryan Sands
    •  & Alexander Mendenhall
  • Article
    | Open Access

    RNA polymerase I (Pol I) catalyses the transcription of pre-ribosomal RNA and for transcription initiation Pol I assembles with core factor and Rrn3 on the rDNA core promoter. Here the authors provide insights into the molecular mechanism of promoter opening by Pol I by determining the cryo-EM structures of two closed, two intermediate and two open Pol I pre-initiation complexes.

    • Yashar Sadian
    • , Florence Baudin
    •  & Christoph W. Müller
  • Article
    | Open Access

    Skewing of X chromosome inactivation (XCI) occurs when the silencing of one parental X chromosome is non-random. Here, Zito et al. report XCI patterns in lymphoblastoid cell lines, blood, subcutaneous adipose tissue samples and skin samples of monozygotic and dizygotic twins and find XCI skew to associate with tissue and age.

    • Antonino Zito
    • , Matthew N. Davies
    •  & Kerrin S. Small
  • Article
    | Open Access

    Transcription initiation involves the coordinated assembly and activity of large multimeric complexes. Here the authors report on the chaperone-mediated ordered assembly of the SAGA and NuA4 transcription co-activator complexes in fission yeast, providing insight into the de novo assembly of transcriptional complexes and the contribution of dedicated chaperones to this process.

    • Alberto Elías-Villalobos
    • , Damien Toullec
    •  & Dominique Helmlinger
  • Article
    | Open Access

    LncRNA loci potentially contain multiple modes that can exert function, including DNA regulatory elements. Here, the authors generated genetic models in mice to dissect the role of the syntenically conserved lncRNA Firre in the context of hematopoiesis.

    • Jordan P. Lewandowski
    • , James C. Lee
    •  & John L. Rinn
  • Article
    | Open Access

    Mutations associated with SCN5A, which encodes the major cardiac sodium channel, influence impulse conduction and are associated with arrhythmia disorders. Here, the authors identify an evolutionary conserved, super enhancer-like, regulatory cluster downstream of SCN5A and show that it controls the chromatin architecture of the locus and Scn5a expression.

    • Joyce C. K. Man
    • , Rajiv A. Mohan
    •  & Vincent M. Christoffels
  • Article
    | Open Access

    Mapping transcription factors (TFs) occupancy is essential for understanding transcriptional programs. Here the authors use biotinylated knockin alleles of key cardiac TFs (GATA4, NKX2-5, MEF2A, MEF2C, SRF, TBX5, TEAD1) to map their genome-wide occupancy in the fetal and adult mouse heart, providing insight into the cardiac transcriptional regulatory network.

    • Brynn N. Akerberg
    • , Fei Gu
    •  & William T. Pu
  • Article
    | Open Access

    Topoisomerase 2 (Top2) is known to resolve DNA topological stress through double strand breaks (DSBs), yet Top2 inhibition has been reported to result in a significant amount of single-strand breaks (SSBs). Here the authors develop CC-seq—a method that allows direct mapping of both Top2-linked SSBs and DSBs—and reveal a significant impact of primary DNA sequence on Top2 directed cleavage.

    • William H. Gittens
    • , Dominic J. Johnson
    •  & Matthew J. Neale
  • Article
    | Open Access

    Trophectoderm lineage development is essential for implantation, placentation, and healthy pregnancy. Here the authors map super-enhancers (SEs) in trophoblast stem cells and find both TE-specific master regulators and 150 previous uncharacterised transcription factors that are SE-associated, providing insight into trophectoderm-specific regulatory networks.

    • Bum-Kyu Lee
    • , Yu jin Jang
    •  & Jonghwan Kim
  • Article
    | Open Access

    In-depth functional characterization of genomes relies on comprehensive transcriptome data. Here, the authors employ four complementary RNA sequencing technologies to explore the transcription landscape across 16 tissues or different organ types in diploid A genome cotton using a newly developed computational pipeline.

    • Kun Wang
    • , Dehe Wang
    •  & Yuxian Zhu
  • Article
    | Open Access

    Gene dosage anomalies such as those caused by aneuploidy underlie diseases including Down syndrome. Here, the authors perform allele-specific single cell transcriptome analysis to investigate the mechanisms of gene dosage imbalance in fibroblasts with trisomies T21, T18, T13 and T8.

    • Georgios Stamoulis
    • , Marco Garieri
    •  & Stylianos E. Antonarakis
  • Article
    | Open Access

    H3K56Ac promotes nucleosome turnover at promoter-proximal locations and assembly of new nucleosomes during S phase. Here the authors find that H3K56Ac is both a genome-wide activator of transcription in yeast while also repressing promiscuous transcription that occurs after replication fork passage.

    • Salih Topal
    • , Pauline Vasseur
    •  & Craig L. Peterson
  • Article
    | Open Access

    The increasing accessibility of single cell RNA sequencing demands tools that enable data visualization and interpretation. Here, the authors introduce Vision, a flexible annotation tool that operates directly on the manifold of cell-cell similarity and aids interpretation of cellular heterogeneity.

    • David DeTomaso
    • , Matthew G. Jones
    •  & Nir Yosef
  • Article
    | Open Access

    The family of DNA methyltransferases (Dnmts) consists of four catalytically active enzymes that catalyze DNA methylation and also play a role as transcriptional regulators. Here the authors show that catalytically inactive Dnmt3b rescues a majority of methylation and expression changes in the absence of Dnmt3b during mouse embryonic development.

    • Pawel Nowialis
    • , Katarina Lopusna
    •  & Rene Opavsky
  • Article
    | Open Access

    In plants, 3′ Pol II pausing helps prevent transcriptional interference. Here the authors provide evidence that BORDER proteins are enriched in intergenic regions and inhibit transcriptional interference between closely spaced genes by preventing RNA polymerase from intruding into the promoters of nearby downstream genes.

    • Xuhong Yu
    • , Pascal G. P. Martin
    •  & Scott D. Michaels
  • Article
    | Open Access

    Age-related tissue alterations have been associated with a decline in stem cell number and function. Here the authors report a single cell multi-omics study of mouse muscle stem cells, combining single cell transcriptome and DNA methylome profiling and find that aged cells have a global increase of uncoordinated transcriptional heterogeneity biased towards genes regulating cell-niche interactions.

    • Irene Hernando-Herraez
    • , Brendan Evano
    •  & Wolf Reik
  • Article
    | Open Access

    Embryonic development produces different cell types in response to a small number of inductive signals. Here, the authors characterise how maternal factors modify chromatin to specify initial competence in Xenopus tropicalis, finding that the pioneering activity of the pluripotency factors Pou5f3 and Sox3 establishes competence for germ layer formation by remodelling chromatin before the onset of signalling.

    • George E. Gentsch
    • , Thomas Spruce
    •  & James C. Smith
  • Article
    | Open Access

    Persistently low levels of estimated glomerular filtration rate (eGFR) are a biomarker of chronic kidney disease. Here, the authors reinterpret the genetic architecture of kidney function across ancestries, to identify not only genes, but the tissue and anatomical contexts of renal homeostasis.

    • Jacklyn N. Hellwege
    • , Digna R. Velez Edwards
    •  & Adriana M. Hung
  • Article
    | Open Access

    Sleep disturbance is common in psychiatric disease, and this may contribute to altered circadian rhythm in gene expression. Here the authors show that rhythms in gene expression in the dorsolateral prefrontal cortex in schizophrenia are different to that seen in healthy controls.

    • Marianne L. Seney
    • , Kelly Cahill
    •  & Colleen A. McClung
  • Article
    | Open Access

    The position, shape and number of transcription start sites (TSS) regulate gene expression. Here authors present MAPCap, a method for high-resolution detection and differential expression analysis of TSS, and apply MAPCap to early fly development, detecting stage and sex-specific promoter and enhancer activity.

    • Vivek Bhardwaj
    • , Giuseppe Semplicio
    •  & Asifa Akhtar
  • Article
    | Open Access

    PIWI-interacting RNAs (piRNAs) are ~25–33 nt small RNAs expressed in animal germ cells. Here, the authors develop a single-cell small RNA sequencing method and report that a class of ~20-nt piRNAs lacking 3′ end 2′-O-methylation are associated with PIWIL3 protein and predominantly expressed in human and monkey oocytes.

    • Qiyuan Yang
    • , Ronghong Li
    •  & Ligang Wu
  • Article
    | Open Access

    Many genetic variants identified in genome-wide association studies are associated with gene expression. Here, Porcu et al. propose a transcriptome-wide summary statistics-based Mendelian randomization approach (TWMR) that, applied to 43 human traits, uncovers hundreds of previously unreported gene–trait associations.

    • Eleonora Porcu
    • , Sina Rüeger
    •  & Zoltán Kutalik
  • Article
    | Open Access

    Tissue- and cell type-specific information helps to interpret findings from genome-wide association studies. Here, the authors leverage multiple single cell expression datasets to infer cell type specificity of traits.

    • Kyoko Watanabe
    • , Maša Umićević Mirkov
    •  & Danielle Posthuma
  • Article
    | Open Access

    Quantifying the effects of noise in gene expression is difficult since noise and mean expression are coupled. Here the authors determine fitness landscapes in mean-noise expression space to uncouple these two parameters and show that changes in noise and mean expression are similarly detrimental to fitness.

    • Jörn M. Schmiedel
    • , Lucas B. Carey
    •  & Ben Lehner
  • Article
    | Open Access

    In prostate cancer, investigating aberrant gene expression may shed light on disease etiology. Here, the authors imputed expression transcriptome-wide for 233,955 European ancestry men, discovering and replicating the associations between prostatic expression for select genes and prostate cancer risk, including the highly prevalent gene fusion partner TMPRSS2. The authors furthermore integrate diverse functional genomic datasets to interpret the epigenetic mechanisms by which the implicated risk variants and genes modulate disease risk.

    • Nima C. Emami
    • , Linda Kachuri
    •  & John S. Witte
  • Article
    | Open Access

    Dosage compensation (DC) on the X chromosome has predictable effects on genetic and phenotypic trait variance. Here, the authors use information for 20 quantitative traits in the UK Biobank and across-tissue gene expression to compare X-linked heritability and the effects of trait-associated SNPs between the sexes.

    • Julia Sidorenko
    • , Irfahan Kassam
    •  & Peter M. Visscher
  • Article
    | Open Access

    The transcriptional signature of embryonic lethality has not been defined. Here, the authors, as part of the Deciphering the Mechanisms of Developmental Disorders programme, define genes causing murine embryonic lethality around E9.5 and identify developmental delay transcriptional signatures.

    • John E. Collins
    • , Richard J. White
    •  & Elisabeth M. Busch-Nentwich
  • Article
    | Open Access

    The genetic and pathogenetic basis of heart failure is incompletely understood. Here, the authors present a high-fidelity tissue collection from rapidly preserved failing and non-failing control hearts which are used for eQTL mapping and network analysis, resulting in the prioritization of PPP1R3A as a heart failure gene.

    • Pablo Cordero
    • , Victoria N. Parikh
    •  & Euan A. Ashley
  • Article
    | Open Access

    Simulated single cell RNA sequencing data is useful for method development and comparison. Here, the authors developed SymSim, a simulator that explicitly models the main factors of variation in single cell data.

    • Xiuwei Zhang
    • , Chenling Xu
    •  & Nir Yosef
  • Article
    | Open Access

    Gene expression dysregulation domains (GEDDs) have been reported in Down syndrome (DS) cells, where changes in gene expression are clustered. Here the authors find that, while GEDDs are present in DS cells and in the Dp1Tyb mouse model of DS, GEDDs do not depend on the DS genotype and occur whenever gene expression changes, suggesting they result from the clustering of co-regulated genes as a function of mammalian genome organisation.

    • Helena Ahlfors
    • , Nneka Anyanwu
    •  & Victor L. J. Tybulewicz
  • Article
    | Open Access

    GWAS have identified risk loci for osteoarthritis (OA), but the causal variants still have to be determined. Here, the authors apply a massively-parallel reporter assay to screen 1,605 candidate SNPs in 35 OA loci, which prioritizes six SNPs in four loci, one of which, rs4730222, is characterized in more detail.

    • Jason C. Klein
    • , Aidan Keith
    •  & Jay Shendure
  • Article
    | Open Access

    Receptor tyrosine kinases localize to the cell surface and have been suggested to also have nuclear function. Here the authors provide evidence that Colony Stimulating Factor-1 Receptor (CSF-1R) migrates to the nucleus upon CSF-1 stimulation in monocytes and that upon differentiation into macrophages, CSF-1R localizes to TSS, co-localizes with H3K4me3, and interacts with ELK and YY1.

    • Laura Bencheikh
    • , M’Boyba Khadija Diop
    •  & Nathalie Droin
  • Article
    | Open Access

    The increasing accessibility of single cell omics technologies beyond transcriptomics demands parallel advances in analysis. Here, the authors introduce STREAM, a pipeline for reconstruction and visualization of differentiation trajectories from both single-cell RNA-seq and ATAC-seq data.

    • Huidong Chen
    • , Luca Albergante
    •  & Luca Pinello
  • Article
    | Open Access

    Although Krüppel-associated box zinc finger proteins (KZFPs) were found to mostly repress transposable elements, recent studies found that KFZPs also play other roles in cells. Here, the authors provide evidence that the KZFP ZFP30 promotes adipogenesis by targeting and activating a retrotransposon-derived Pparg2 enhancer in cooperation with co-regulator KRAB-associated protein 1 (KAP1).

    • Wanze Chen
    • , Petra C. Schwalie
    •  & Bart Deplancke
  • Article
    | Open Access

    Diagnosis and classification of peripheral neuropathy (PN) is facilitated by nerve conduction (NC) studies. Here, Bjornsdottir et al. find a low-frequency PRPH splice-donor variant that associates with NC amplitude and neurological assessment of recalled PRPH variant carriers reveals increased risk of a mild sensory-negative PN.

    • Gyda Bjornsdottir
    • , Erna V. Ivarsdottir
    •  & Kari Stefansson