Gene expression

  • Review Article |

    This review describes the state of spatial transcriptomics technologies and analysis tools that are being used to generate biological insights in diverse areas of biology.

    • Anjali Rao
    • , Dalia Barkley
    •  & Itai Yanai
  • Article |

    Mapping enhancer regulation across human cell types and tissues illuminates genome function and provides a resource to connect risk variants for common diseases to their molecular and cellular functions.

    • Joseph Nasser
    • , Drew T. Bergman
    •  & Jesse M. Engreitz
  • Article |

    An ultra-high-throughput multiplex protein–DNA binding assay is used to assess binding of 270 human transcription factors to 95,886 noncoding variants in the human genome, providing data to improve prediction of the effects of noncoding variants on transcription factor binding and thereby increase understanding of molecular pathways involved in diverse human traits and genetic diseases.

    • Jian Yan
    • , Yunjiang Qiu
    •  & Bing Ren
  • Article |

    An analysis using ribosome-profiling and matched RNA-sequencing data for three organs across five mammalian species and a bird enables the comparison of translatomes and transcriptomes, revealing patterns of co-evolution of these two expression layers.

    • Zhong-Yi Wang
    • , Evgeny Leushkin
    •  & Henrik Kaessmann
  • Article
    | Open Access

    Single-cell and single-nucleus RNA sequencing are used to construct a cellular atlas of the human heart that will aid further research into cardiac physiology and disease.

    • Monika Litviňuková
    • , Carlos Talavera-López
    •  & Sarah A. Teichmann
  • Article |

    The histone variant H3.3 is phosphorylated at Ser31 in induced genes, and this selective mark stimulates the histone methyltransferase SETD2 and ejects the ZMYND11 repressor, thus revealing a role for histone phosphorylation in amplifying de novo transcription.

    • Anja Armache
    • , Shuang Yang
    •  & Steven Z. Josefowicz
  • Article |

    Bulk RNA sequencing of organs and plasma proteomics at different ages across the mouse lifespan is integrated with data from the Tabula Muris Senis, a transcriptomic atlas of ageing mouse tissues, to describe organ-specific changes in gene expression during ageing.

    • Nicholas Schaum
    • , Benoit Lehallier
    •  & Tony Wyss-Coray
  • Article |

    Single-cell transcriptomics of more than 20,000 cells from two functionally distinct areas of the mouse neocortex identifies 133 transcriptomic types, and provides a foundation for understanding the diversity of cortical cell types.

    • Bosiljka Tasic
    • , Zizhen Yao
    •  & Hongkui Zeng
  • Article |

    A genetic atlas of the human plasma proteome, comprising 1,927 genetic associations with 1,478 proteins, identifies causes of disease and potential drug targets.

    • Benjamin B. Sun
    • , Joseph C. Maranville
    •  & Adam S. Butterworth
  • Letter |

    RNA polymerase III is a key evolutionarily conserved regulator of longevity that may have potential as a therapeutic target for age-related conditions.

    • Danny Filer
    • , Maximillian A. Thompson
    •  & Nazif Alic
  • Letter
    | Open Access

    The authors show that rare genetic variants contribute to large gene expression changes across diverse human tissues and provide an integrative method for interpretation of rare variants in individual genomes.

    • Xin Li
    • , Yungil Kim
    •  & Stephen B. Montgomery
  • Letter |

    Gene expression analysis in brain tissue from individuals with and without autism spectrum disorder (ASD) suggests that the transcription factor SOX5 contributes to an ASD-associated reduction in transcriptional differences between brain areas and indicates that common transcriptomic changes occur in different forms of ASD.

    • Neelroop N. Parikshak
    • , Vivek Swarup
    •  & Daniel H. Geschwind
  • Letter |

    Atherosclerotic lesions in mice and humans switch on a ‘don’t eat me’ signal—expression of CD47—that prevents effective removal of diseased tissue; anti-CD47 antibody therapy can normalize this defective efferocytosis, with beneficial results in several mouse models of atherosclerosis.

    • Yoko Kojima
    • , Jens-Peter Volkmer
    •  & Nicholas J. Leeper
  • Letter |

    Preclinical evaluation and optimization of mitochondrial replacement therapy reveals that a modified form of pronuclear transfer is likely to give rise to normal pregnancies with a reduced risk of mitochondrial DNA disease, but may need further modification to eradicate the disease in all cases.

    • Louise A. Hyslop
    • , Paul Blakeley
    •  & Mary Herbert
  • Letter |

    Translation termination sequences are occasionally bypassed by the ribosome and the resulting proteins can be detrimental to the cell; here it is shown that cells can prevent such proteins from accumulating through peptides that are encoded within the 3' UTR of genes in both humans and C. elegans.

    • Joshua A. Arribere
    • , Elif S. Cenik
    •  & Andrew Z. Fire
  • Letter |

    Splicing factors such as BUD31 are identified in a synthetic-lethal screen with cells overexpressing the transcription factor MYC; oncogenic MYC leads to an increase in pre-mRNA synthesis, and spliceosome inhibition impairs the growth and tumorigenicity of MYC-dependent breast cancers, suggesting that spliceosome components may be potential therapeutic targets for MYC-driven cancers.

    • Tiffany Y.-T. Hsu
    • , Lukas M. Simon
    •  & Thomas F. Westbrook
  • Letter |

    Quantifying activity of cis-regulatory sequences controlling gene expression shows that selection on expression noise has a greater impact on sequence variation than selection on mean expression level.

    • Brian P. H. Metzger
    • , David C. Yuan
    •  & Patricia J. Wittkopp
  • Letter
    | Open Access

    As part of the Epigenome Roadmap project, this study uses a chromosome-spanning haplotype reconstruction strategy to construct haplotype-resolved epigenomic maps for a diverse set of human tissues; the maps reveal extensive allelic biases in chromatin state and transcription, which vary across individuals due to genetic backgrounds.

    • Danny Leung
    • , Inkyung Jung
    •  & Bing Ren
  • Letter |

    Disruption of lignin biosynthesis has been proposed as a way to improve forage and bioenergy crops, but it can result in stunted growth and developmental abnormalities; here, the undesirable features of one such manipulation are shown to depend on the transcriptional co-regulatory complex Mediator.

    • Nicholas D. Bonawitz
    • , Jeong Im Kim
    •  & Clint Chapple
  • Letter |

    Epistasis has rarely been shown among natural polymorphisms in human traits; this research using advanced computation and gene expression data reveals many instances of epistasis between common single nucleotide polymorphisms in humans, with epistasis and the direction of its effect replicating in independent cohorts.

    • Gibran Hemani
    • , Konstantin Shakhbazov
    •  & Joseph E. Powell
  • Article |

    Evolutionary study of long noncoding RNA (lncRNA) repertoires and expression patterns in 11 tetrapod species identifies approximately 11,000 primate-specific lncRNAs and 2,500 highly conserved lncRNAs, including approximately 400 genes that are likely to have ancient origins; many lncRNAs, particularly ancient ones, are actively regulated and may function mainly in embryonic development.

    • Anamaria Necsulea
    • , Magali Soumillon
    •  & Henrik Kaessmann
  • Letter |

    Exploration of the interacting effect of statin exposure and genetic variation on gene expression identifies a cis-eQTL that is differentially associated with expression of the GATM gene, which encodes a rate-limiting enzyme involved in creatine synthesis, and that is associated with incidence of statin-induced myopathy, the major adverse effect of statin treatment.

    • Lara M. Mangravite
    • , Barbara E. Engelhardt
    •  & Ronald M. Krauss
  • Article |

    Transient overexpression of the transcription factors NKX2-1 and PAX8 in a murine cell model is shown to direct the differentiation of embryonic stem cells towards a thyroid follicular cell lineage; the resulting three-dimensional thyroid follicles created by subsequent thyrotropin treatment show hallmarks of thyroid function in vitro and rescue thyroid function in vivo when transplanted into athyroid mice, adding to our understanding of the molecular mechanisms underlying thyroid development.

    • Francesco Antonica
    • , Dominika Figini Kasprzyk
    •  & Sabine Costagliola
  • Brief Communications Arising |

    • Pontus Boström
    • , Jun Wu
    •  & Bruce M. Spiegelman
  • Letter |

    APJ is shown to be a bifunctional receptor for both mechanical stretch and the endogenous peptide apelin, a finding that is important for the development of APJ agonists to treat heart failure.

    • Maria Cecilia Scimia
    • , Cecilia Hurtado
    •  & Pilar Ruiz-Lozano
  • Letter |

    A genomic map of nearly 300,000 potential cis-regulatory sequences determined from diverse mouse tissues and cell types reveals active promoters, enhancers and CCCTC-binding factor sites encompassing 11% of the mouse genome and significantly expands annotation of mammalian regulatory sequences.

    • Yin Shen
    • , Feng Yue
    •  & Bing Ren
  • Letter |

    In a mouse model of mammary carcinoma, loss of deleted in colorectal cancer (DCC) promotes metastasis formation, and in cell cultures derived from p53-deficient mouse mammary tumours DCC expression controls netrin-1-dependent cell survival, supporting the function of DCC as a context-dependent tumour suppressor that limits survival of disseminated tumour cells.

    • Paul Krimpenfort
    • , Ji-Ying Song
    •  & Anton Berns