Gene expression

  • Article
    | Open Access

    Notch receptor GLP-1 is required for maintaining germ cells in the C. elegans germline. Here the authors show that syndecan-1, a somatic transmembrane proteoglycan regulates expression of glp-1 and germ cell mitosis in C. elegans, by promoting calcium-dependent binding of APTF-2 to the glp-1 promoter.

    • Sandeep Gopal
    • , Aqilah Amran
    •  & Roger Pocock
  • Article
    | Open Access

    @melkebir @psashittal et al. develop a graph-based method for the assembly of discontinuous transcripts produced in Coronaviruses and other Nidovirales, enabling the discovery of transcriptional changes missed by existing methods.

    • Palash Sashittal
    • , Chuanyi Zhang
    •  & Mohammed El-Kebir
  • Article
    | Open Access

    Age is associated with increasing vulnerability to both acute and chronic lung diseases. Employing genomic analysis and live lung imaging, this study reveals a profile of increased cellular senescence, telomere shortening, and fibrosis-induced impaired alveolar function in the natural history of human lung aging.

    • Seoyeon Lee
    • , Mohammad Naimul Islam
    •  & Mallar Bhattacharya
  • Article
    | Open Access

    Here the authors identify PHF3 SPOC domain as a reader of the phosphorylated RNA polymerase II (Pol II) C-terminal domain. They show that PHF3 clusters with Pol II complexes in cells, drives phase separation of Pol II in vitro, and regulates neuronal gene expression and neuronal differentiation.

    • Lisa-Marie Appel
    • , Vedran Franke
    •  & Dea Slade
  • Article
    | Open Access

    Annotating functional elements of the genome helps the interpretation of genetic variation. Here, the authors compile functional genomics data for the pig genome over 14 tissues with 15 different chromatin states, integrate the data with WGS and GWAS data, and compare conservation of regulatory elements across mouse and human tissues.

    • Zhangyuan Pan
    • , Yuelin Yao
    •  & Huaijun Zhou
  • Article
    | Open Access

    CHARGE syndrome that affects cerebellar development can be caused by haploinsufficiency of the chromatin remodeling enzyme CHD7; however the precise role of CHD7 remains unknown. Here the authors show CHD7 promotes chromatin accessibility and enhancer activity in granule cell precursors and regulates morphogenesis of the cerebellar cortex, where loss of CHD7 triggers cerebellar polymicrogyria.

    • Naveen C. Reddy
    • , Shahriyar P. Majidi
    •  & Harrison W. Gabel
  • Article
    | Open Access

    How to infer transient cells and cell-fate transitions from snap-shot single cell transcriptome dataset remains a major challenge. Here the authors present a multiscale approach to construct single-cell dynamical manifold, quantify cell stability, and compute transition trajectory and probability between cell states.

    • Peijie Zhou
    • , Shuxiong Wang
    •  & Qing Nie
  • Article
    | Open Access

    The BMP antagonist Gremlin1 balances BMP and SHH signalling, endowing limb bud development with robustness. Here, the authors identify enhancers controlling Grem1 levels in an additive, and spatial regulation in a synergistic manner, providing digit patterning with cis-regulatory robustness and evolutionary plasticity.

    • Jonas Malkmus
    • , Laurène Ramos Martins
    •  & Rolf Zeller
  • Article
    | Open Access

    TFE3-translocation renal cell carcinoma (TFE3-tRCC) is a rare subtype of kidney cancer with no standard treatment options for the advanced disease. Here, the authors perform genomic and transcriptomic profiling of 63 untreated primary TFE3-tRCC tumours and reveal potential therapeutic targets.

    • Guangxi Sun
    • , Junru Chen
    •  & Hao Zeng
  • Article
    | Open Access

    The global pattern of the mammalian methylome is formed by changes in methylation and demethylation. Here the authors describe a metric methylation concurrence that measures the ratio of unmethylated CpGs inside the partially methylated reads and show that methylation concurrence is associated with epigenetically regulated tumour suppressor genes.

    • Jiejun Shi
    • , Jianfeng Xu
    •  & Wei Li
  • Article
    | Open Access

    The effect of histone H4 lysine 20 methylation (H4K20me) on chromatin accessibility are not well established. Here the authors show how H4K20 methylation regulates chromatin structure and accessibility to ensure precise transcriptional outputs through the cell cycle using genome-wide approaches, in vitro biophysical assays, and NMR.

    • Muhammad Shoaib
    • , Qinming Chen
    •  & Claus S. Sørensen
  • Article
    | Open Access

    Genetic mechanisms underlying fetal hemoglobin (HbF) regulation and switching are not fully understood. Here, the authors develop a single-cell genome editing functional assay to model how effects of mutation-harbouring functional elements contribute to HbF expression.

    • Yong Shen
    • , Jeffrey M. Verboon
    •  & Vijay G. Sankaran
  • Article
    | Open Access

    Lineage tracing and snapshots of transcriptional state at the single-cell level are powerful, complementary tools for studying development. Here, the authors propose a mathematical method combining lineage tracing with trajectory inference to improve our understanding of development.

    • Aden Forrow
    •  & Geoffrey Schiebinger
  • Article
    | Open Access

    Local gene co-expression is found throughout the genome, but systematic analysis of these co-expressed genes is needed. Here, the authors identify local co-expressed genes in 49 tissues and characterize the genetic variants which may affect their expression and contribute to disease.

    • Diogo M. Ribeiro
    • , Simone Rubinacci
    •  & Olivier Delaneau
  • Article
    | Open Access

    The ability of HIV to alternate between acute and latent forms is thought to rely on a transcriptional feedback loop where polymerase pausing is released by the viral protein Tat. Here, the authors show that viral genome transcription can occur in a burst-like stochastic manner in the absence of Tat.

    • Katjana Tantale
    • , Encar Garcia-Oliver
    •  & Edouard Bertrand
  • Article
    | Open Access

    In most mammals, imprinted genes contain epigenetic marks that differ in each parental genome and control their parent-of-origin-specific expression. Here, the authors map imprinted genes in mouse preimplantation embryos and find that imprinted gene expression in blastocysts is mainly dependent on Polycomb-mediated H3K27me3-associated gene silencing.

    • Laura Santini
    • , Florian Halbritter
    •  & Martin Leeb
  • Article
    | Open Access

    A comprehensive transcriptomic survey of the pig could enable mechanistic understanding of tissue specialization and accelerate its use as a biomedical model. Here the authors characterize four distinct transcript types in 31 adult pig tissues to dissect their distinct structural and transcriptional features and uncover transcriptomic variability related to tissue physiology.

    • Long Jin
    • , Qianzi Tang
    •  & Mingzhou Li
  • Article
    | Open Access

    The transcription factor BRN2 regulates melanoma migration and invasion, but its role during melanoma initiation is unclear. Here the authors show that BRN2 is a haplo-insufficient tumour suppressor that positively regulates PTEN expression and in the context of BRAF mutation and heterozygous PTEN, BRN2 loss promotes melanoma initiation and progression.

    • Michael Hamm
    • , Pierre Sohier
    •  & Lionel Larue
  • Article
    | Open Access

    Single cell RNA-seq loses spatial information of gene expression in multicellular systems because tissue must be dissociated. Here, the authors show the spatial gene expression profiles can be both accurately and robustly reconstructed by a new computational method using a generative linear mapping, Perler.

    • Yasushi Okochi
    • , Shunta Sakaguchi
    •  & Honda Naoki
  • Article
    | Open Access

    Allele-specific expression in diploid organisms can be quantified by RNA-seq and it is common practice to rely on a single library. Here, the authors show that the standard approach has variable error rate and present Qllelic as a tool to improve reproducibility of allele-specific RNA-seq analysis.

    • Asia Mendelevich
    • , Svetlana Vinogradova
    •  & Alexander A. Gimelbrant
  • Article
    | Open Access

    The heterogeneity of tumor evolution from AR-positive, adenocarcinoma to AR-negative, neuroendocrine prostate cancer (NEPC) is not fully characterized. Here the authors generate a mouse model to show that Rb1 loss and MYCN overexpression accelerates the progression to AR-negative NEPC and identify emergence of distinct subpopulations of NEPC cells.

    • Nicholas J. Brady
    • , Alyssa M. Bagadion
    •  & David S. Rickman
  • Article
    | Open Access

    Homeostasis of the intestinal epithelium is crucial for the maintenance of the epithelial barrier. Here, the authors show that mir-802 ablation in the mouse intestine impairs enterocyte differentiation and glucose absorption, enhances Paneth cell function by increasing Tmed9-mediated defensin secretion, and increases epithelial cell turnover.

    • Algera Goga
    • , Büsra Yagabasan
    •  & Markus Stoffel
  • Article
    | Open Access

    Microglia associated with Aβ plaques may have a distinct transcriptional signature compared to those in plaque-free areas of the brain in Alzheimer’s disease (AD) models. Here the authors show that amyloid plaque phagocytosis is associated with a specific microglia transcriptional signature in a mouse model of AD.

    • Alexandra Grubman
    • , Xin Yi Choo
    •  & Jose M. Polo
  • Article
    | Open Access

    While coffee and tea consumption has been associated with risk of diseases, their mechanisms of action remain elusive. Here the authors present a large EWAS on coffee and tea consumption in cohorts of European and African-American ancestries, finding that coffee consumption is associated with differential DNA methylation levels at multiple CpGs.

    • Irma Karabegović
    • , Eliana Portilla-Fernandez
    •  & Mohsen Ghanbari
  • Article
    | Open Access

    Classification methods for scRNA-seq data are limited in their ability to learn from multiple datasets simultaneously. Here the authors present scHPL, a hierarchical progressive learning method that automatically finds relationships between cell populations across multiple datasets and constructs a classification tree.

    • Lieke Michielsen
    • , Marcel J. T. Reinders
    •  & Ahmed Mahfouz
  • Article
    | Open Access

    Placental dysfunction can have catastrophic or barely discernible effects ranging from miscarriage to apparently normal birth. Here the authors present a comprehensive analysis of the human placental transcriptome and identify circular RNAs and piRNAs.

    • Sungsam Gong
    • , Francesca Gaccioli
    •  & D. Stephen Charnock-Jones
  • Article
    | Open Access

    A fundamental principle of evolutionary theory is that the force of natural selection is weaker on traits expressed late in life relative to traits expressed early. Here, the authors find strong and consistent patterns of molecular evolution reflecting this principle in four species of animals, including humans.

    • Changde Cheng
    •  & Mark Kirkpatrick
  • Article
    | Open Access

    Selection on alleles contributing to human evolution is not well understood. Here, the authors investigate positive selection on skin barrier adaptation, identifying a selective sweep on involucrin alleles associated with migration out of Africa, and confirming enhancer regulatory effects with functional assays.

    • Mary Elizabeth Mathyer
    • , Erin A. Brettmann
    •  & Cristina de Guzman Strong
  • Article
    | Open Access

    Whether chronic inflammation contributes to metabolic disease through the dysregulation of circadian systems remains incompletely understood in humans. Here the authors show that circadian clock function is perturbed in adipose tissue from individuals with obesity, and that inhibition of NFkB improves clock function.

    • Eleonore Maury
    • , Benoit Navez
    •  & Sonia M. Brichard
  • Article
    | Open Access

    PU.1 is a master regulator of myeloid development but its role in disease-relevant neutrophils is not well known. Here, the authors look at primary neutrophils from a human population and find that genetic variants affecting binding of PU.1 are associated with cell count and disease susceptibility.

    • Stephen Watt
    • , Louella Vasquez
    •  & Nicole Soranzo
  • Article
    | Open Access

    Conventional single-cell RNA sequencing analysis rely on genome annotations that may be incomplete or inaccurate especially for understudied organisms. Here the authors present a bioinformatic tool that leverages single-cell data to uncover biologically relevant transcripts beyond the best available genome annotation.

    • Michael F. Z. Wang
    • , Madhav Mantri
    •  & Iwijn De Vlaminck
  • Article
    | Open Access

    Variable number tandem repeats (VNTRs) are implicated in human diseases yet have been difficult to analyse computationally. Here, the authors describe a neural network method, adVNTR-NN, that allows rapid and accurate genotyping of VNTRs from large whole genome sequencing datasets.

    • Mehrdad Bakhtiari
    • , Jonghun Park
    •  & Vineet Bafna
  • Article
    | Open Access

    The demethylase FTO was shown to remove on N6-methyladenosine (m6A) and N6, 2’-O-dimethyladenosine (m6Am) modifications on RNAs. Here the authors show that FTO impedes cancer stem cell-like abilities in colorectal cancer cells through its m6Am demethylase activity, not through internal m6A demethylase activity.

    • Sébastien Relier
    • , Julie Ripoll
    •  & Alexandre David
  • Article
    | Open Access

    The SWI/SNF complex BAF and the histone H3K4 methyltransferase MLL4 (KMT2D) play critical roles in enhancer activation, however the interplay between them has remained unclear. Here the authors show that BAF and MLL4 are interdependent in promoting enhancer activation by lineage-determining transcription factors during adipogenesis.

    • Young-Kwon Park
    • , Ji-Eun Lee
    •  & Kai Ge
  • Article
    | Open Access

    The question as to how the soma regulates the germline has been much studied. Here, the authors show in C. elegans that the poly-U specific endoribonuclease ENDU-2 is secreted from the soma and taken-up by the germline, binding mature mRNA, repressing expression of somatic transcripts and maintaining germline immortality.

    • Wenjing Qi
    • , Erika D. V. Gromoff
    •  & Ralf Baumeister