Epigenetics analysis articles within Nature Reviews Genetics

Featured

  • Review Article |

    In this Review, the authors discuss the latest advances in profiling multiple molecular modalities from single cells, including genomic, transcriptomic, epigenomic and proteomic information. They describe the diverse strategies for separately analysing different modalities, how the data can be computationally integrated, and approaches for obtaining spatially resolved data.

    • Katy Vandereyken
    • , Alejandro Sifrim
    •  & Thierry Voet

  • Review Article |

    The ability to map DNA and RNA modifications has improved our understanding of these marks, but in some cases inconsistent results have been problematic. Here, Kong et al. discuss how to recognize and resolve issues associated with commonly used sequencing-based approaches to minimize mapping errors.

    • Yimeng Kong
    • , Edward A. Mead
    •  & Gang Fang

  • Review Article |

    In this Review, Preissl, Gaulton and Ren discuss single-cell epigenomic methods and data analysis tools, their readiness for profiling cis-regulatory elements in human tissues and the insight they can provide into dynamic, context-specific gene regulation.

    • Sebastian Preissl
    • , Kyle J. Gaulton
    •  & Bing Ren

  • Review Article |

    In this Review, Boulias and Greer provide an overview of current approaches for detecting and mapping N6-methyl-2′-deoxyadenosine (6mA or m6dA), and discuss the evidence for its presence and functional importance in the genomes of multicellular eukaryotes.

    • Konstantinos Boulias
    •  & Eric Lieberman Greer

  • In Brief |

    Kong et al. describe 6mASCOPE, a new approach for both quantifying N6-methyldeoxyadenine (6mA) and discriminating its genomic source. Results indicate that eukaryotic genomes contain low levels of 6mA, with bacterial genomes accounting for the majority of 6mA in some samples.

    • Dorothy Clyde

  • Perspective |

    In this Perspective article, Oh and Petronis discuss emerging evidence of time-dependent patterns of DNA modification and describe how incorporating this ‘chrono-epigenetic’ perspective could add value and interpretability in human disease studies.

    • Edward Saehong Oh
    •  & Art Petronis

  • Research Highlight |

    A new study in Science uses chromatin accessibility profiles to reveal gene regulatory alterations associated with genetic variants in neuropsychiatric disease.

    • Darren J. Burgess

  • Research Highlight |

    Two studies in Molecular Cell report fine-scale structural profiles of mammalian genomes using Micro-C, indicating that fine chromosomal structure is regulated by diverse transcription-related features.

    • Darren J. Burgess

  • Comment |

    Direct-to-consumer epigenetic tests have the potential to reveal sensitive information about individuals, such as disease risk and exposure history. Yet regulation lags behind purely genetics-based tests. In this Comment article, the authors discuss the salient ethical and legal considerations of direct-to-consumer epigenetic tests.

    • Charles Dupras
    • , Elisabeth Beauchamp
    •  & Yann Joly

  • Review Article |

    Recent methodological advances have driven the identification and characterization of cis-acting long non-coding RNAs (lncRNAs), which modulate target gene expression through various mechanisms and operate at various genomic distances. This Review discusses recent insights into the evolution and functions of these cis-acting lncRNAs.

    • Noa Gil
    •  & Igor Ulitsky

  • Research Highlight |

    A study in Nature Genetics shows that genomic rearrangements that cause extensive changes to chromatin topology do not alter expression for the majority of genes.

    • Linda Koch

  • Research Highlight |

    A study in Nature Methods describes a light-activated dynamic looping (LADL) system, which consists of a synthetic architectural protein that rapidly induces long-range chromatin interactions in response to blue light.

    • Linda Koch

  • Review Article |

    Enabled by genome-wide profiling approaches, there is growing appreciation for the prevalence and functional importance of various types of chromatin-associated RNAs. As Li and Fu describe in this Review, these RNAs can either be retained in cis at their site of transcription or recruited in cis to other loci, and they have diverse roles in gene regulation, genome organization, nuclear body formation and phase-separation events.

    • Xiao Li
    •  & Xiang-Dong Fu

  • Review Article |

    For appropriate control of gene expression, enhancers must communicate with the right target genes at the right time, typically over large genomic distances. In this Review, Schoenfelder and Fraser discuss our latest understanding of long-range enhancer–promoter crosstalk, including target-gene specificity, interaction dynamics, protein and RNA architects of interactions, roles of 3D genome organization and the pathological consequences of regulatory rewiring.

    • Stefan Schoenfelder
    •  & Peter Fraser

  • Review Article |

    Chromatin accessibility comprises the positions, compaction and dynamics of nucleosomes, as well as the occupancy of DNA by other proteins such as transcription factors. In this Review, the authors discuss diverse methods for characterizing chromatin accessibility, how accessibility is determined and remodelled in cells and the regulatory roles of accessibility in gene expression and development.

    • Sandy L. Klemm
    • , Zohar Shipony
    •  & William J. Greenleaf

  • Review Article |

    Disruptions to the epigenome occur during the pathogenesis of various human diseases. In this Review, Berdasco and Esteller describe the challenges and progress of harnessing epigenetic changes for clinical application, including for diagnostics, disease classification and therapeutics. They discuss applications to diverse diseases, such as cancer, neurological disease, immune disorders and viral infections.

    • María Berdasco
    •  & Manel Esteller

  • Research Highlight |

    A study in Cell examines the pervasiveness of a classic form of non-genetic inheritance involving transposable element DNA methylation in mice. It reports that non-genetic inheritance is likely to be the exception rather than the rule across other loci genome-wide.

    • Darren J. Burgess

  • Research Highlight |

    A study in Nature Medicine reports the DNA methylome and transcriptome of an individual, and suggests that changes in the methylome and transcriptome might be associated with chronic and acute health conditions, respectively.

    • Katharine H. Wrighton

  • Research Highlight |

    A study in Science reports the genome-wide chromatin accessibility profiles across 23 cancer types from The Cancer Genome Atlas and notably increases the number of known gene regulatory elements.

    • Michelle Trenkmann

  • Perspective |

    High-resolution studies of chromosome conformation are revealing that the 3D genome is organized into smaller structural features than was previously supposed and is primarily composed of compartmental domains and CTCF loops. In this Perspectives article Rowley and Corces describe the latest views on the organizational drivers and principles of the 3D genome, and the interplay between genome activity and organization.

    • M. Jordan Rowley
    •  & Victor G. Corces

  • Research Highlight |

    A paper in Cell presents split–pool recognition of interactions by tag extension (SPRITE), a method that enables the identification of multiple, simultaneously occurring DNA and RNA interactions genome-wide within the nucleus.

    • Linda Koch

  • Review Article |

    The wealth of DNA methylation data continues to grow rapidly, including from epigenome-wide association studies (EWAS). However, extracting meaningful biological and clinical information requires diverse computational approaches for data analysis. This Review discusses the range of statistical tools available, including for cell-type deconvolution, identification of important methylation data features, causation and system-level integration with other types of omic data.

    • Andrew E. Teschendorff
    •  & Caroline L. Relton

  • Opinion |

    Epigenome-wide association studies (EWAS) are potentially powerful approaches for identifying transcriptional regulatory perturbations (particularly DNA methylation) that associate with phenotypes of interest. In this Opinion article, Lappalainen and Greally provide their views on how to maximize the interpretability and biological insights from these associations, such as by hypothesis-driven consideration of cellular phenotypes, characterizing the roles of transcription factors, dissecting directions of causality and moving towards multi-omics profiling.

    • Tuuli Lappalainen
    •  & John M. Greally

  • Review Article |

    A key mode of regulating DNA methylation is through active demethylation driven by TET-mediated oxidation of 5-methylcytosine (5mC). This Review discusses our latest understanding of the mechanisms and regulation of active DNA demethylation, and the roles of active demethylation (and the oxidized 5mC intermediates) in gene regulation, genome stability, development and disease.

    • Xiaoji Wu
    •  & Yi Zhang

  • Review Article |

    A full understanding of chromatin in diverse cellular processes requires the consideration of its dynamics, but most standard chromatin assays provide only a static snapshot. This Review describes various emerging methods for probing chromatin dynamics across a wide range of temporal and spatial scales, and discusses the resulting biological insights.

    • Olivier Cuvier
    •  & Beat Fierz

  • Review Article |

    Although it has been known for decades that RNA is subjected to numerous covalent modifications, there has been a recent surge in interest driven by sequencing-based transcriptome-wide detection methods and the realization that RNA modifications have important roles in diverse biological processes. This Review describes the range of detection strategies for RNA modifications, their particular strengths and limitations, and how responsible and complementary application of these techniques will be required to ensure the quality and interpretability of the rapidly accumulating data sets.

    • Mark Helm
    •  & Yuri Motorin

  • Review Article |

    During the cell cycle, the centromeres of chromosomes have important roles and face key challenges, such as mediating successful chromosome segregation during mitosis and faithfully propagating their chromatin state to daughter chromosomes during S phase. This Review describes cell cycle-related features of centromeres, focusing on the nature and dynamics of centromeric chromatin, how it is intricately regulated and the potential implications for disease when these processes are disrupted.

    • Sebastian Müller
    •  & Geneviève Almouzni

  • Review Article |

    A wealth of data is emerging from diverse studies of epigenomics, including genome-scale profiles of DNA methylation, histone modifications and higher-order chromatin features. In this Review, the authors discuss how, despite all this information, many challenges remain for inferring and proving the physiological and pathological functions of chromatin states. They describe the degrees of 'functionality' that are revealed by different experimental approaches, the value of integrative strategies and visions for the future.

    • Stefan H. Stricker
    • , Anna Köferle
    •  & Stephan Beck

  • Review Article |

    In this article the authors review current knowledge on chromatin architecture and the molecular mechanisms that underlie it. They discuss how three-dimensional (3D) organization of chromatin relates to gene expression, development and disease, and consider its effect on genome evolution.

    • Boyan Bonev
    •  & Giacomo Cavalli

  • Analysis |

    Evidence is emerging that transcription factors (TFs) lacking methyl-CpG binding domains can interact with methylated DNA. This Analysis article reviews thein vitro and in vivoevidence for methylation-mediated interactions between TFs and DNA, and their functional consequences.

    • Heng Zhu
    • , Guohua Wang
    •  & Jiang Qian

  • Review Article |

    Various methodologies have been developed to characterize diverse features of chromatin, but understanding how epigenomic states contribute to cellular heterogeneity requires adoption of these techniques at the single-cell level. This article discusses the technological developments driving single-cell epigenomics, including the practical and bioinformatic challenges and emerging biological insights.

    • Omer Schwartzman
    •  & Amos Tanay

  • Review Article |

    The resolution of epigenomic profiling has been vastly augmented with the adoption of new approaches to interrogate varied features of the epigenome. This Review describes these techniques and outlines the ways in which these genome-wide tools can be used to examine the epigenome.

    • Gabriel E. Zentner
    •  & Steven Henikoff

  • Review Article |

    Next-generation sequencing methods can be used to examine features of chromatin biology, although the outputs of these methods can be subject to various potential biases. This Review describes the ways in which biases can be introduced to such experiments and outlines methods to detect and mitigate their effect.

    • Clifford A. Meyer
    •  & X. Shirley Liu

  • Review Article |

    Recent developments and refinements to DNA methylation assays have led to the availability of several methods to detect and quantify cytosine modifications. This Review discusses the principles behind the newly developed techniques, compares the strengths and weaknesses of the different methods, and provides guidelines for selecting the most appropriate methods for particular experimental contexts.

    • Nongluk Plongthongkum
    • , Dinh H. Diep
    •  & Kun Zhang

  • Review Article |

    Mapping DNA methylation is vital for understanding the importance of this epigenetic mark in health and disease. Recent years have seen rapid progress in the development of techniques for genome-scale methylation profiling; this Review introduces and evaluates the available methods.

    • Peter W. Laird

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