Reviews & Analysis

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  • Nuclear receptors are transcription factors that transduce hormonal, nutrient, metabolite and redox signals into regulation of metabolic genes, in particular the transcriptional control of energy metabolism. Accordingly, nuclear receptors have central roles in adapting gene expression to changing energetic demands, thereby maintaining cellular energy homeostasis

    • Charlotte Scholtes
    • Vincent Giguère
    Review Article
  • Histone H3 Lys9 (H3K9)-methylated heterochromatin ensures transcriptional silencing of repetitive elements and genes, and its deregulation leads to impaired cell and tissue identity, premature aging and cancer. Recent studies in mammals clarified the roles H3K9-specific histone methyltransferases in ensuring transcriptional homeostasis during tissue differentiation.

    • Jan Padeken
    • Stephen P. Methot
    • Susan M. Gasser
    Review Article
  • Abiotic stresses, such as drought, salinity, heat, cold and flooding, have profound effects on plant growth and survival. Adaptation and tolerance to such stresses require sophisticated sensing, signalling and stress response mechanisms. Shroeder and colleagues discuss recent insights into how plant hormones control such responses. Understanding these mechanisms opens opportunities for agricultural applications.

    • Rainer Waadt
    • Charles A. Seller
    • Julian I. Schroeder
    Review Article
  • Nuclei are subject to various deformations, being pulled, pushed, squeezed and stretched by a plethora of intracellular and extracellular forces. Recent work is unravelling how nuclei sense and respond to these deformations, including with changes in genome organization and function, cell signalling, and cell mechanics.

    • Yohalie Kalukula
    • Andrew D. Stephens
    • Sylvain Gabriele
    Review Article
  • Nuclear transcription of a wide variety of RNA species is conducted mainly by three RNA polymerases, which are large and dynamic protein complexes. Recent structural studies have provided important insights into the activities at different transcription stages and the commonalities and differences between these transcription machineries.

    • Mathias Girbig
    • Agata D. Misiaszek
    • Christoph W. Müller
    Review Article
  • RNA–DNA hybrids and R-loop structures are widespread during transcription, replication and DNA repair. R-loops regulate gene expression, but their unfettered accumulation causes genome instability and contributes to neurodegeneration and cancer. Recent mechanistic understanding of R-loop suppression provides therapeutic opportunities to target them.

    • Eva Petermann
    • Li Lan
    • Lee Zou
    Review Article
  • Apical–basal polarity is essential for epithelial cell form and function. Elucidating how distinct apical and basolateral compartments are established and maintained is essential to better understand the roles of apical–basal cell polarization in morphogenesis and how defects in polarity contribute to diseases such as cancer.

    • Clare E. Buckley
    • Daniel St Johnston
    Review Article
  • The configuration of microtubule networks is cell type-specific and strongly correlates with cell function and behaviour. The regulation of microtubule nucleation, dynamics and distribution all contribute to the establishment and remodelling of these functionally diverse microtubule architectures.

    • Anna Akhmanova
    • Lukas C. Kapitein
    Review Article
  • Mechanical signalling underlies multiple, fundamental biological processes. Mechanical signals can originate from substrate physical properties or shear stresses, and from changes in the physical properties of the cell surface. The mechanisms underlying these two classes of outside-in signalling and their roles in the regulation of intracellular signalling in cell fate and development are becoming increasingly understood.

    • Henry De Belly
    • Ewa K. Paluch
    • Kevin J. Chalut
    Review Article
  • Pioneer transcription factors activate gene enhancers through their unique ability to initiate opening of inaccessible chromatin. Pioneer factors are crucial for cell fate determination in development and for cellular reprogramming, and their misexpression has major pathological consequences in cancer.

    • Aurelio Balsalobre
    • Jacques Drouin
    Review Article
  • Extracellular vesicles (EVs) mediate cell–cell communication in physiology and pathology but many questions remain about the mechanisms governing their delivery to recipient cells. This Expert Recommendation article highlights areas of progress and challenges in establishing the importance of EV-mediated communication in vivo.

    • Guillaume van Niel
    • David R. F. Carter
    • Pieter Vader
    Expert Recommendation
  • Topoisomerases have essential roles in transcription, DNA replication, chromatin remodelling and, as recently revealed, 3D genome organization. However, topoisomerases also generate DNA–protein crosslinks coupled with DNA breaks, which are increasingly recognized as a source of disease-causing genomic damage.

    • Yves Pommier
    • André Nussenzweig
    • Caroline Austin
    Review Article
  • The regulatory sequences carried by transposable elements (TEs) often recruit the transcription machinery and affect host gene expression. Recent studies have revealed mechanisms by which TEs contribute to transcription regulation, including donation of enhancer and promoter sequences, modification of 3D chromatin architecture, and generation of novel regulatory non-coding RNAs and transcription factors.

    • Raquel Fueyo
    • Julius Judd
    • Joanna Wysocka
    Review Article
  • The metabolism of somatic stem cells must be regulated to meet their specific needs, to enable long-term maintenance as well as their activation, proliferation and subsequent differentiation. Better understanding of metabolic regulation in stem cells will open new opportunities to manipulate stem cell function, with potential applications in tissue regeneration and cancer prevention.

    • Corbin E. Meacham
    • Andrew W. DeVilbiss
    • Sean J. Morrison
    Review Article
  • Reactive oxygen species (ROS) comprise a wide variety of oxidant molecules with vastly different properties and biological functions in physiology and in disease. Approaches to characterize oxidants in the in vivo context and identify their specific cellular targets will be required to understand and control the pathophysiological activities of ROS.

    • Helmut Sies
    • Vsevolod V. Belousov
    • Christine Winterbourn
    Expert Recommendation
  • E3 ubiquitin ligases ensure the precise spatiotemporal control of key molecules during important cellular processes. This Review discusses the crucial roles of E3 ligases during early mammalian development and their roles in human disease, and considers how new methods to manipulate the ubiquitin regulatory machinery — for example, the development of molecular glues and PROTACs — might facilitate clinical therapy.

    • David A. Cruz Walma
    • Zhuoyao Chen
    • Kenneth M. Yamada
    Review Article
  • Mammalian RNA polymerase II transcribes protein-coding genes and non-coding transcription units, including long non-coding RNAs (lncRNAs). Studies applying recently developed nascent transcriptomics technology have revealed differences in transcription initiation and termination between lncRNAs and protein-coding genes, bearing relevance to genomic stress and DNA damage.

    • Takayuki Nojima
    • Nick J. Proudfoot
    Review Article
  • The majority of macromolecules are transported across the nuclear membrane by the Karyopherin-β (Kap) proteins, comprising importins, exportins and biportins. Unravelling mechanisms and regulation of Kap–cargo interactions is essential for understanding nuclear export and import of proteins and RNA and how this traffic impacts their physiological functions.

    • Casey E. Wing
    • Ho Yee Joyce Fung
    • Yuh Min Chook
    Review Article
  • Lysine acetyltransferases and lysine deacetylases regulate gene expression and protein function by controlling acetylation and deacetylation of histones and diverse non-histone proteins. The activity of lysine acetyltransferases and lysine deacetylases is regulated by cellular metabolic states, offering the potential for therapeutic modulation through dietary and pharmacological interventions.

    • Maria Shvedunova
    • Asifa Akhtar
    Review Article
  • X chromosome inactivation in mammals involves chromosome-wide gene silencing at one X chromosome in cells of females, a process that requires complex spatiotemporal regulation. Recent findings provide new insights into the mechanisms and dynamics of X chromosome inactivation and the accompanying 3D reshaping of the chromosome.

    • Agnese Loda
    • Samuel Collombet
    • Edith Heard
    Review Article