Epigenomics

  • Article
    | Open Access

    A comprehensive survey of the epigenome from 45 regions of the mouse cortex, hippocampus, striatum, pallidum and olfactory areas using single-nucleus DNA methylation sequencing enables identification of 161 cell clusters with distinct locations and projection targets and provides insights into the regulatory landscape underlying neuronal diversity and spatial regulation.

    • Hanqing Liu
    • , Jingtian Zhou
    •  & Joseph R. Ecker
  • Article
    | Open Access

    Quantitative analysis of the methylation of mouse cortical neurons that project to different cortical and subcortical target regions provides insight into genetic mechanisms that contribute to differences in cell function.

    • Zhuzhu Zhang
    • , Jingtian Zhou
    •  & Edward M. Callaway
  • 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 |

    A comprehensive map of transcriptomes, cis-regulatory elements, heterochromatin structure, the methylome and 3D genome organization in the zebrafish (Danio rerio) enables identification of species-specific and evolutionarily conserved regulatory features, and provides a foundation for modelling studies on human disease and development.

    • Hongbo Yang
    • , Yu Luan
    •  & Feng Yue
  • Article |

    Analysis of cis-regulatory chromatin interactions, open chromatin and transcriptomes for different cell types isolated from mid-gestational human cortex samples provides insights into gene regulation during development.

    • Michael Song
    • , Mark-Phillip Pebworth
    •  & Yin Shen
  • Perspective
    | Open Access

    The authors summarize the history of the ENCODE Project, the achievements of ENCODE 1 and ENCODE 2, and how the new data generated and analysed in ENCODE 3 complement the previous phases.

    • Federico Abascal
    • , Reyes Acosta
    •  & Richard M. Myers
  • Article
    | Open Access

    ChIP–seq and CETCh–seq data are used to analyse binding maps for 208 transcription factors and other chromatin-associated proteins in a single human cell type, providing a comprehensive catalogue of the transcription factor landscape and gene regulatory networks in these cells.

    • E. Christopher Partridge
    • , Surya B. Chhetri
    •  & Eric M. Mendenhall
  • Article |

    An experimental and analytical pipeline is used to assess, at the single-cell level, complex transcriptional and morphological mutant phenotypes that occur in mouse embryos during gastrulation.

    • Stefanie Grosswendt
    • , Helene Kretzmer
    •  & Alexander Meissner
  • Article |

    Structural cells implement a broad range of immune-regulatory functions beyond their roles as barriers and connective tissues, and they utilize an epigenetically encoded potential for immune gene activation in their rapid response to viral infection.

    • Thomas Krausgruber
    • , Nikolaus Fortelny
    •  & Christoph Bock
  • Article |

    Single-cell mapping of chromatin accessibility, DNA methylation and RNA expression during gastrulation in mouse embryos shows characteristic epigenetic changes that accompany formation of the primary germ layers.

    • Ricard Argelaguet
    • , Stephen J. Clark
    •  & Wolf Reik
  • Letter |

    A single-cell approach is used to follow the heritable stochastic changes to DNA methylation that occur in primary chronic lymphocytic leukaemia and healthy B cells, allowing the tracing of cell lineage histories and evolution during treatment with ibrutinib.

    • Federico Gaiti
    • , Ronan Chaligne
    •  & Dan A. Landau
  • Letter |

    A strategy using droplet-based and barcode-linked sequencing captures multiplex chromatin interactions at single-molecule precision, and here provides topological insight into chromatin structures and transcription in Drosophila.

    • Meizhen Zheng
    • , Simon Zhongyuan Tian
    •  & Yijun Ruan
  • Letter |

    Gonadal germline epigenetic reprogramming involves an interplay between DNA methylation, the polycomb complex and Tet1 in both DNA methylation dependent and independent roles, to ensure the activation of a specific subset of genes critical for progression of gametogenesis.

    • Peter W. S. Hill
    • , Harry G. Leitch
    •  & Petra Hajkova
  • Perspective |

    The 4D Nucleome Network aims to map the spatial and dynamic organization of the human and mouse genomes to gain insight into the structure and biological functions of the nucleus.

    • Job Dekker
    • , Andrew S. Belmont
    •  & Sheng Zhong
  • 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 |

    Three papers in this issue of Nature use highly sensitive ChIP–seq assays to describe the dynamic patterns of histone modifications during early mouse embryogenesis, showing that oocytes have a distinctive epigenome and providing insights into how the maternal gene expression program transitions to the zygotic program.

    • Bingjie Zhang
    • , Hui Zheng
    •  & Wei Xie
  • Article |

    An improved ATAC-seq approach is used to describe a genome-wide view of accessible chromatin and cis-regulatory elements in mouse preimplantation embryos, allowing construction of a regulatory network of early development that helps to identify key modulators of lineage specification.

    • Jingyi Wu
    • , Bo Huang
    •  & Wei Xie
  • Article |

    The prevalence of N6-adenine DNA methylation in mammals was previously unknown; this study reveals that N6-methyladenine can be found in mouse embryonic stem cells, especially at subfamilies of young (<1.5 million years old) LINE-1 transposons.

    • Tao P. Wu
    • , Tao Wang
    •  & Andrew Z. Xiao
  • Letter |

    Genome-wide binding profiles for eight different chromatin remodellers in mouse embryonic stem (ES) cells are determined at single nucleosome resolution; each remodeller binds at specific nucleosome positions relative to the start of genes, and the same remodeller acts as a positive or negative regulator of transcription depending on the promoter chromatin organization and epigenetic marking of the gene it binds.

    • Maud de Dieuleveult
    • , Kuangyu Yen
    •  & Matthieu Gérard
  • Letter |

    This study demonstrates a role for the Integrator complex in the stimulus-dependent induction of eRNAs and their 3′ processing; together with previously known roles of Integrator in transcription elongation and RNA processing, these results indicate that Integrator has broad functions in the regulation of eukaryotic gene expression.

    • Fan Lai
    • , Alessandro Gardini
    •  & Ramin Shiekhattar
  • Letter |

    A single-cell method for probing genome-wide chromatin accessibility has been developed; the results provide insight into the relationship between cell-to-cell variation associated with specific trans-factors and cis-elements, as well insights into the relationship between chromatin accessibility and three-dimensional genome organization.

    • Jason D. Buenrostro
    • , Beijing Wu
    •  & William J. Greenleaf
  • Letter
    | Open Access

    As part of the Epigenome Roadmap Project, genome-wide maps of DNA methylation and transcriptomes together with genomic DNA sequencing of 18 different primary human tissue types from 4 individuals are presented; analysis reveals widespread differential methylation of CG sites between tissues, and the presence of non-CG methylation in adult tissues.

    • Matthew D. Schultz
    • , Yupeng He
    •  & Joseph R. Ecker
  • Article
    | Open Access

    This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

    • Anshul Kundaje
    • , Wouter Meuleman
    •  & Manolis Kellis
  • 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
  • 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
    | Open Access

    An analysis of genome-wide chromatin interactions during human embryonic stem cell differentiation reveals changes in chromatic organization and simultaneously identifies allele-resolved chromatin structure and differences in gene expression during differentiation.

    • Jesse R. Dixon
    • , Inkyung Jung
    •  & Bing Ren
  • Article
    | Open Access

    The Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types; these data were compared with those from human to confirm substantial conservation in the newly annotated potential functional sequences and to reveal pronounced divergence of other sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization.

    • Feng Yue
    • , Yong Cheng
    •  & Bing Ren
  • Article |

    Genome-wide association studies combined with data from epigenomic maps for immune cells have been used to fine-map causal variants for 21 autoimmune diseases; disease risk tends to be linked to single nucleotide polymorphisms in cell-type-specific enhancers, often in regions adjacent to transcription factor binding motifs.

    • Kyle Kai-How Farh
    • , Alexander Marson
    •  & Bradley E. Bernstein
  • Letter
    | Open Access

    A large collection of new modENCODE and ENCODE genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human are analysed; this reveals many conserved features of chromatin organization among the three organisms, as well as notable differences in the composition and locations of repressive chromatin.

    • Joshua W. K. Ho
    • , Youngsook L. Jung
    •  & Peter J. Park