Review Articles

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  • This Review discusses strategies for the genetic engineering of adoptive T cell immunotherapies with a focus on approaches harnessing transgenic T cell receptors or chimeric antigen receptors to treat cancer. The authors also discuss the more complex levels of genetic regulation that will be needed to ensure both safety and efficacy.

    • Gavin I. Ellis
    • Neil C. Sheppard
    • James L. Riley
    Review Article
  • Interactions between microorganisms and their hosts are highly context dependent and contribute to both normal tissue function and infectious disease pathology. In this Review, Westermann and Vogel describe how advances in RNA sequencing techniques are providing molecular insights into host–microbe interactions, including advances in cross-species and single-cell transcriptomics.

    • Alexander J. Westermann
    • Jörg Vogel
    Review Article
  • There is a rapidly growing appreciation of the complexities of 3D genome organization, as well as associations with gene expression and wider cellular and organismal phenotypes, including diseases. In this Review, the authors describe diverse experimental methods for manipulating 3D genome organization — from fine-scale control of DNA contacts to large-scale nuclear repositioning — which are facilitating detailed testing of the biological functions of 3D genome organization.

    • Haifeng Wang
    • Mengting Han
    • Lei S. Qi
    Review Article
  • Maintenance of cell-type identity requires the faithful inheritance of chromatin states through cell division, despite the challenges posed by the disruptive passage of the DNA replication fork and the dilution of nucleosome components in complex with the daughter DNA strands. In this Review, Escobar, Loyola and Reinberg discuss how methodological advances are providing unprecedented mechanistic insights into the segregation of parental nucleosomes, how these mechanisms maintain gene expression programmes and how non-faithful nucleosome segregation is linked to differentiation and disease.

    • Thelma M. Escobar
    • Alejandra Loyola
    • Danny Reinberg
    Review Article
  • MicroRNAs (miRNA) exert essential functions in mammalian development and physiology. The authors review recent insights from the phenotypic analysis of miRNA knockouts in mice that emphasize roles for these non-coding RNAs at different developmental stages and in adults, and illustrate the importance of functional miRNA targets, miRNA dosage, miRNA interactions and cellular context.

    • Brian DeVeale
    • Jennifer Swindlehurst-Chan
    • Robert Blelloch
    Review Article
  • Shadow enhancers regulate a common target gene and drive expression patterns that overlap spatiotemporally. The authors review recent insights into the prevalence and role of shadow enhancers in metazoans, as well as their mechanisms of action to fine-tune gene expression. They also discuss the evolution of shadow enhancers and their implication in disease.

    • Evgeny Z. Kvon
    • Rachel Waymack
    • Zeba Wunderlich
    Review Article
  • Africa is a continent with deep evolutionary history, which has implications for the genetic underpinnings of disease. In this Review, the authors discuss how genetic features of African populations provide both challenges and opportunities for understanding disease genetics in Africa. They describe how this genetic knowledge — combined with initiatives including capacity-building, data sharing and increased representation of African genomes in genetic variation databases — can be leveraged towards achieving precision medicine approaches in African healthcare.

    • Luisa Pereira
    • Leon Mutesa
    • Michèle Ramsay
    Review Article
  • Our evolutionary history has resulted in highly complex and sophisticated human physiology. Yet evolutionary footprints have also left us prone to diseases. In this Review, the authors discuss how events from the earliest history of life on Earth through to modern human evolution influence many disease traits and outcomes. They describe how an understanding and application of evolutionary frameworks can inform precision medicine initiatives.

    • Mary Lauren Benton
    • Abin Abraham
    • John A. Capra
    Review Article
  • The ability to reprogramme cellular translation and genomes to produce non-canonical biopolymers has wide-ranging applications, including in therapeutics, but has yet to be fully realized. In this Review, de la Torre and Chin discuss recent advances towards achieving this goal.

    • Daniel de la Torre
    • Jason W. Chin
    Review Article
  • Haematopoietic stem and progenitor cell (HSPC) gene therapy using lentiviral or gammaretroviral vectors has now been approved for clinical use. In this Review, Ferrari, Thrasher and Aiuti discuss the history of HSPC gene therapy, the clinical promise of gene-editing HPSCs and the use of HSPC gene therapy to treat specific diseases.

    • Giuliana Ferrari
    • Adrian J. Thrasher
    • Alessandro Aiuti
    Review Article
  • Infectious diseases are an ever-present global threat. In this Review, Kwok, Mentzer and Knight discuss our latest understanding of how human genetics influence susceptibility to disease. Furthermore, they discuss emerging progress in the interplay between host and pathogen genetics, molecular responses to infection and vaccination, and opportunities to bring these aspects together for rapid responses to emerging diseases such as COVID-19.

    • Andrew J. Kwok
    • Alex Mentzer
    • Julian C. Knight
    Review Article
  • In this Review, Carter and Zhao discuss how single-cell sequencing technologies are being applied to investigate epigenetic heterogeneity among seemingly homogeneous populations of cells and how this epigenetic variability relates to cell–cell differences in gene expression.

    • Benjamin Carter
    • Keji Zhao
    Review Article
  • RNA-binding proteins (RBPs) are critical effectors of gene expression, and their malfunction underlies many diseases. The authors review the role of RBPs in human genetic disorders, both Mendelian and somatic, discuss the molecular mechanisms of disease and highlight emerging therapeutic interventions that target RBPs.

    • Fátima Gebauer
    • Thomas Schwarzl
    • Matthias W. Hentze
    Review Article
  • In this Review, Oudelaar and Higgs discuss the relationship between genome structure and gene regulation, with a focus on whether genome organization has an instructive role or largely reflects the activity of regulatory elements.

    • A. Marieke Oudelaar
    • Douglas R. Higgs
    Review Article
  • Cell–cell interactions and communication can be inferred from RNA sequencing data of, for example, ligand–receptor pairs. The authors review insights gained and the methods and tools used in studies of cell–cell interactions based on transcriptomic data.

    • Erick Armingol
    • Adam Officer
    • Nathan E. Lewis
    Review Article
  • The effects of genetic variation on the adaptive potential of species depend on the frequencies of alleles at other loci in the individual or in the population, and the patterns of spatio-temporal co-occurrence between alleles in interacting species. This Review explores these population and community genomic contexts and their direct and indirect effects on biodiversity, ecosystems and people.

    • Madlen Stange
    • Rowan D. H. Barrett
    • Andrew P. Hendry
    Review Article
  • Deep resequencing has revealed extreme genetic variation in mitochondrial genomes at multiple levels. This heterogeneity has implications for the origins of human mitochondrial DNA mutations as well as their impact on rare and common human diseases, including cancer.

    • James B. Stewart
    • Patrick F. Chinnery
    Review Article
  • In this Review, Cenik and Shilatifard focus on two families of Trithorax group proteins: COMPASS histone H3 lysine 4 methyltransferase complexes and SWI/SNF chromatin remodelling complexes. They discuss the roles of these complexes in gene regulation, development and disease.

    • Bercin K. Cenik
    • Ali Shilatifard
    Review Article
  • Various cellular metabolites provide the chemical moieties for DNA and histone modifications, resulting in a complex interplay between metabolism and epigenetics. In this Review, Dai, Ramesh and Locasale discuss the metabolic regulation of diverse types of chromatin modifications and the functional consequences of these modifications at the molecular, cellular and organismal levels, as well as influences from diet and microbiota.

    • Ziwei Dai
    • Vijyendra Ramesh
    • Jason W. Locasale
    Review Article