Transcriptional regulatory elements articles within Nature

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  • Article
    | Open Access

    Low-affinity transcription factor binding sites are prevalent across the genome, and single nucleotide changes that increase binding affinity even slightly can cause gain-of-function gene expression and phenotypes (such as polydactyly).

    • Fabian Lim
    • , Joe J. Solvason
    •  & Emma K. Farley

  • Article
    | Open Access

    Whole-genome alignment of 239 primate species reveals noncoding regulatory elements that are under selective constraint in primates but not in other placental mammals, that are enriched for variants that affect human gene expression and complex traits in diseases.

    • Lukas F. K. Kuderna
    • , Jacob C. Ulirsch
    •  & Kyle Kai-How Farh

  • Article
    | Open Access

    Cryo-EM structures and analysis provide insight into the mechanisms by which basic helix–loop–helix transcription factors access E-box DNA sequences that are embedded within nucleosomes, and cooperate with other transcription factors.

    • Alicia K. Michael
    • , Lisa Stoos
    •  & Nicolas H. Thomä

  • Article
    | Open Access

    Binding of the human pioneer transcription factor OCT4 to nucleosomes containing endogenous DNA sequences causes changes to the nucleosome structure and facilitates the cooperative assembly of multiple pioneer transcription factors, a property that can be affected by histone modifications.

    • Kalyan K. Sinha
    • , Silvija Bilokapic
    •  & Mario Halic

  • Article |

    Subunits of SWI/SNF act as mitotic bookmarks to safeguard cell identity during cell division.

    • Zhexin Zhu
    • , Xiaolong Chen
    •  & Charles W. M. Roberts

  • Article |

    A high throughput recruitment assay testing the transcriptional activity of more than 100,000 protein fragments tiling across most human chromatin regulators and transcription factors maps the locations and strengths of activation, repression and bifunctional domains, and identifies the sequences necessary for these functions.

    • Nicole DelRosso
    • , Josh Tycko
    •  & Lacramioara Bintu

  • Article |

    The nuclear mitotic apparatus protein NuMA helps to protect genes from oxidative damage by occupying regions around transcription start sites, binding DNA repair factors and promoting transcription following damage.

    • Swagat Ray
    • , Arwa A. Abugable
    •  & Sherif F. El-Khamisy

  • Article |

    The systematic categorization of human enhancers by their cofactor dependencies provides a conceptual framework to understand the sequence and chromatin diversity of enhancers and their roles in different gene-regulatory programmes.

    • Christoph Neumayr
    • , Vanja Haberle
    •  & Alexander Stark

  • Article |

    In Drosophila, there are extensive physical and functional associations of distant paralogous genes, including co-regulation by shared enhancers and co-transcriptional initiation over distances of nearly 250 kilobases.

    • Michal Levo
    • , João Raimundo
    •  & Michael S. Levine

  • Article
    | Open Access

    A study maps neuronal genomic targets of oestrogen receptor-α and shows how they coordinate brain sexual differentiation, concluding that the genome remains responsive to hormonal changes after structural dimorphisms have been established.

    • B. Gegenhuber
    • , M. V. Wu
    •  & J. Tollkuhn

  • Article
    | Open Access

    The transcriptional effect of an enhancer depends on its contact probabilities with the promoter through a nonlinear relationship, and enhancer strength determines absolute transcription levels as well as the sensitivity of a promoter to CTCF-mediated transcriptional insulation.

    • Jessica Zuin
    • , Gregory Roth
    •  & Luca Giorgetti

  • Article |

    Disruption of a promoter can release its partner enhancer to activate other promoters in the same contact domain, and this process, named ‘enhancer release and retargeting’, can often lead to gene alterations that cause disease.

    • Soohwan Oh
    • , Jiaofang Shao
    •  & Michael G. Rosenfeld

  • Article |

    A ChIP–exo method is used to define the genome-wide positional organization of proteins associated with gene transcription, DNA replication, centromeres, subtelomeres and transposons, revealing distinct protein assemblies for constitutive and inducible gene expression.

    • Matthew J. Rossi
    • , Prashant K. Kuntala
    •  & B. Franklin Pugh

  • 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 |

    RNA polymerase II has an unexpected function in the nucleolus, helping to drive the expression of ribosomal RNA and to protect nucleolar structure through a mechanism involving triplex R-loop structures.

    • Karan J. Abraham
    • , Negin Khosraviani
    •  & Karim Mekhail

  • Article |

    ERK reversibly regulates embryonic stem cell transcription via selective redistribution of co-factors and RNA polymerase from pluripotency to early differentiation enhancers, while leaving transcription factors bound to their enhancers, thus preserving plasticity.

    • William B. Hamilton
    • , Yaron Mosesson
    •  & Joshua M. Brickman

  • Letter |

    A screen of 23 transcriptional cofactors for their ability to activate 72,000 candidate core promoters in Drosophila melanogaster identified distinct compatibility groups, providing insight into mechanisms that underlie the selective activation of transcriptional programs.

    • Vanja Haberle
    • , Cosmas D. Arnold
    •  & Alexander Stark

  • Letter |

    Allele-specific single-cell RNA sequencing provides insights into transcription kinetics, with data indicating that core promoter sequences affect burst size, whereas enhancers mainly affect burst frequency.

    • Anton J. M. Larsson
    • , Per Johnsson
    •  & Rickard Sandberg

  • Letter |

    By applying an optimized ATAC-seq protocol to human early embryos, distinct accessible chromatin landscapes are found before and after zygotic genome activation, revealing a marked epigenetic transition during zygotic genome activation and putative regulatory elements wiring human early development.

    • Jingyi Wu
    • , Jiawei Xu
    •  & Yingpu Sun

  • Letter |

    An improved assay for chromatin accessibility at single-cell resolution in Drosophila melanogaster embryos enables identification of developmental-stage- and cell-lineage-specific patterns of chromatin-level transcriptional regulation.

    • Darren A. Cusanovich
    • , James P. Reddington
    •  & Eileen E. M. Furlong

  • Article |

    A technique called genome architecture mapping (GAM) involves sequencing DNA from a large number of thin nuclear cryosections to develop a map of genome organization without the limitations of existing 3C-based methods.

    • Robert A. Beagrie
    • , Antonio Scialdone
    •  & Ana Pombo

  • Letter |

    When transcription and replication machineries collide on DNA, they can cause mutations to occur in the area near the collision; these mutations are now shown to include two types—duplications/deletions within the transcription unit and base substitutions in the cis-regulatory element of gene expression.

    • T. Sabari Sankar
    • , Brigitta D. Wastuwidyaningtyas
    •  & Jue D. Wang

  • Letter |

    The relationship between DNA methylation and transcription factor binding was studied across the genome in mouse embryonic stem cells-the study reveals that the transcription factor NRF1 is methylation-sensitive and how physiological binding of NRF1 relies on local removal of DNA methylation.

    • Silvia Domcke
    • , Anaïs Flore Bardet
    •  & Dirk Schübeler

  • Letter |

    A large-scale enhancer complementation assay assessing the activating or repressing contributions of over 800 Drosophila transcription factors and cofactors to combinatorial enhancer control reveals a more complex picture than expected, with many factors having diverse regulatory functions that depend on the enhancer context.

    • Gerald Stampfel
    • , Tomáš Kazmar
    •  & Alexander Stark

  • Letter |

    A high-throughput analysis of DNA binding in over 9,000 interacting transcription factor pairs reveals that the interactions are often actively mediated by the DNA itself and the composite DNA sites recognized are different from the individual motifs of each transcription factor.

    • Arttu Jolma
    • , Yimeng Yin
    •  & Jussi Taipale

  • Article |

    A CRISPR-Cas9 approach is used to perform saturating mutagenesis of the human and mouse BCL11A enhancers, producing a map that reveals critical regions and specific vulnerabilities; BCL11A enhancer disruption is validated by CRISPR-Cas9 as a therapeutic strategy for inducing fetal haemoglobin by applying it in both mice and primary human erythroblast cells.

    • Matthew C. Canver
    • , Elenoe C. Smith
    •  & Daniel E. Bauer

  • Letter |

    Epistatic interactions, whereby a mutation's effect is contingent on another mutation, have been shown to constrain evolution within single proteins, and how such interactions arise in gene regulatory networks has remained unclear; here the appearance of pheromone-response regulator binding sites in the regulatory DNA of the a-specific genes of Saccharomyces cerevisiae are shown to have required specific changes in a second pathway during the evolution from its common ancestor with Candida albicans.

    • Trevor R. Sorrells
    • , Lauren N. Booth
    •  & Alexander D. Johnson

  • Article
    | Open Access

    Lineage-specific transcription factors and signalling pathways cooperate with pluripotency regulators to control the transcriptional networks that drive cell specification and exit from an embryonic stem cell state; here, we report genome-wide binding data for 38 transcription factors combined with analysis of epigenomic and gene expression data during the differentiation of human embryonic stem cells into the three germ layers.

    • Alexander M. Tsankov
    • , Hongcang Gu
    •  & Alexander Meissner

  • Article |

    The CRISPR-Cas9 system, a powerful tool for genome editing, has been engineered to activate endogenous gene transcription specifically and potently on a genome-wide scale and applied to a large-scale gain-of-function screen for studying melanoma drug resistance.

    • Silvana Konermann
    • , Mark D. Brigham
    •  & Feng Zhang

  • Letter |

    R-loops, which have been considered to be rare and potentially harmful transcriptional by-products, are now shown to be needed for antisense transcription and to induce repressive chromatin marks that reinforce pausing of transcription and thereby enhance its termination.

    • Konstantina Skourti-Stathaki
    • , Kinga Kamieniarz-Gdula
    •  & Nicholas J. Proudfoot

  • Letter |

    The interplay of histone acetylation and RNA polymerase II activity is investigated using fluorescence microscopy; acetylation of H3 at Lys 27 enhances the recruitment of a transcriptional activator and accelerates the transition of RNA polymerase II from initiation to elongation, thus indicating that histone acetylation has a causal effect on two distinct steps in transcription activation.

    • Timothy J. Stasevich
    • , Yoko Hayashi-Takanaka
    •  & Hiroshi Kimura

  • Letter |

    The POU homeodomain transcription factor Pit1 is required for pituitary development; here Pit1-occupied enhancers are shown to interact with the nuclear architecture components matrin-3 and Satb1, and this association is required for activation of Pit1-regulated enhancers and coding target genes.

    • Dorota Skowronska-Krawczyk
    • , Qi Ma
    •  & Michael G. Rosenfeld

  • Letter |

    A high-resolution map of enhancer three-dimensional contacts during Drosophila embryogenesis shows that although local regulatory interactions are frequent, long-range interactions are also very common; unexpectedly, most interactions appear unchanged between tissues and across development and are formed prior to gene expression, indicating that transcription initiates from preformed enhancer–promoter loops, which are associated with paused polymerase.

    • Yad Ghavi-Helm
    • , Felix A. Klein
    •  & Eileen E. M. Furlong

  • Letter |

    Obesity-associated noncoding sequences within FTO are functionally connected with IRX3, and long-range enhancers in this region recapitulate aspects of IRX3 expression, suggesting that the obesity-associated interval is part of IRX3 regulation; Irx3-deficient mice have lower body weight and are resistant to diet-induced obesity, suggesting IRX3 as a novel determinant of body mass and composition.

    • Scott Smemo
    • , Juan J. Tena
    •  & Marcelo A. Nóbrega

  • Letter |

    In the predominantly diploid yeast Saccharomyces cerevisiae, regulatory control of mating is separate from meiosis; here the related hemiascomycete yeast Candida lusitaniae is shown to have coordinated regulatory control of mating and meiosis, favouring the formation of haploids.

    • Racquel Kim Sherwood
    • , Christine M. Scaduto
    •  & Richard J. Bennett

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