Collection |

The 3D genome

The three-dimensional configuration of the genome is complex, dynamic and crucial for gene regulation. In the past few years, technological advances in chromosome conformation capture methods and in microscopy techniques revealed how the organization of the genome is interconnected with nuclear architecture and can vary between cell types and during cell differentiation and development. This collection includes recent articles from across the Nature group of journals and showcases both the latest advances in the methodologies used to study genome organization, and our recent understanding of how genome organization and nuclear architecture regulate gene expression, cell fate and cell function in physiology and disease. The content of this collection has been chosen by the editors of Nature Reviews Molecular Cell Biology.

Reviews

  • Nature Reviews Genetics | Review Article

    Recent studies show that structural variation can alter the genome architecture, leading to changes in the regulation of gene expression that cause disease. The authors review the role of genetic structural variation in disease and the pathogenic potential of changes to the 3D genome.

    • Malte Spielmann
    • , Darío G. Lupiáñez
    •  &  Stefan Mundlos
  • Nature | 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
    • , Mitchell Guttman
    • , Victor O. Leshyk
    • , John T. Lis
    • , Stavros Lomvardas
    • , Leonid A. Mirny
    • , Clodagh C. O’Shea
    • , Peter J. Park
    • , Bing Ren
    • , Joan C. Ritland Politz
    • , Jay Shendure
    • , Sheng Zhong
    •  &  the 4D Nucleome Network
  • Nature Reviews Molecular Cell Biology | Review Article

    Mechanical cues from the microenvironment can be efficiently transmitted to the nucleus to engage in the regulation of genome organization and gene expression. Recent technological and theoretical progress sheds new light on the relationships between cell mechanics, nuclear and chromosomal architecture and gene transcription.

    • Caroline Uhler
    •  &  G. V. Shivashankar
  • Nature Reviews Genetics | Review Article

    Three-dimensional genome organization can shape gene expression by facilitating interactions between regulatory elements. The authors review the process of X-chromosome inactivation with a focus on chromatin organization and subnuclear localization of the active and inactive X chromosomes, as well as the potential roles of long non-coding RNAs.

    • Teddy Jégu
    • , Eric Aeby
    •  &  Jeannie T. Lee
  • Nature Methods | Review Article

    In this Review, the authors compare commonly used chromosome conformation capture techniques, describing their respective strengths and weaknesses, and provide advice for the end user on which approach and analysis method to use.

    • James O J Davies
    • , A Marieke Oudelaar
    • , Douglas R Higgs
    •  &  Jim R Hughes

Research & Methods

  • Nature Genetics | Article

    The authors analyze time-resolved changes in genome topology, gene expression, transcription-factor binding, and chromatin state during iPSC generation. They conclude that 3D genome reorganization generally precedes gene expression changes and that removal of locus-specific topological barriers explains why pluripotency genes are activated sequentially during reprogramming.

    • Ralph Stadhouders
    • , Enrique Vidal
    • , François Serra
    • , Bruno Di Stefano
    • , François Le Dily
    • , Javier Quilez
    • , Antonio Gomez
    • , Samuel Collombet
    • , Clara Berenguer
    • , Yasmina Cuartero
    • , Jochen Hecht
    • , Guillaume J. Filion
    • , Miguel Beato
    • , Marc A. Marti-Renom
    •  &  Thomas Graf
  • Nature Communications | Article | open

    Risk loci for breast cancer have been identified by genome-wide association studies. Here, the authors use Capture Hi-C to identify 110 putative target genes at 33 loci and assessed associations of gene expression, SNP genotype, and survival, providing evidence of mechanisms that may influence the prognosis and risk of breast cancer.

    • Joseph S. Baxter
    • , Olivia C. Leavy
    • , Nicola H. Dryden
    • , Sarah Maguire
    • , Nichola Johnson
    • , Vita Fedele
    • , Nikiana Simigdala
    • , Lesley-Ann Martin
    • , Simon Andrews
    • , Steven W. Wingett
    • , Ioannis Assiotis
    • , Kerry Fenwick
    • , Ritika Chauhan
    • , Alistair G. Rust
    • , Nick Orr
    • , Frank Dudbridge
    • , Syed Haider
    •  &  Olivia Fletcher
  • Nature Communications | Article | open

    Transcriptional regulation is coupled with chromosomal positioning and chromatin architecture. Here the authors develop a transcriptional decomposition approach to separate expression associated with genome structure from independent effects not directly associated with genomic positioning.

    • Sarah Rennie
    • , Maria Dalby
    • , Lucas van Duin
    •  &  Robin Andersson
  • Nature Communications | Article | open

    Super-enhancers (SEs) are important regulatory elements for gene expression, but their intrinsic properties remain poorly understood. Here the authors analyse Hi-C and ChIP-seq data and find that a significant fraction of SEs are hierarchically organized, containing both hub and non-hub enhancers.

    • Jialiang Huang
    • , Kailong Li
    • , Wenqing Cai
    • , Xin Liu
    • , Yuannyu Zhang
    • , Stuart H. Orkin
    • , Jian Xu
    •  &  Guo-Cheng Yuan
  • Nature Methods | Brief Communication

    3DNetMod identifies nested topologically associating domains (TADs) and subTADs from Hi-C data.

    • Heidi K Norton
    • , Daniel J Emerson
    • , Harvey Huang
    • , Jesi Kim
    • , Katelyn R Titus
    • , Shi Gu
    • , Danielle S Bassett
    •  &  Jennifer E Phillips-Cremins
  • Nature Plants | Article

    Knowledge of three-dimensional (3D) genome structure and how polyploidization shapes it remains poor. A study now characterizes and compares 3D genomes for diploid and tetraploid cotton, showing how allopolyploidization affects 3D genome architecture and transcriptional regulation.

    • Maojun Wang
    • , Pengcheng Wang
    • , Min Lin
    • , Zhengxiu Ye
    • , Guoliang Li
    • , Lili Tu
    • , Chao Shen
    • , Jianying Li
    • , Qingyong Yang
    •  &  Xianlong Zhang

Protocols

  • Nature Protocols | Protocol

    This protocol describes targeted chromatin capture (T2C), a high-resolution method to interrogate 3D chromatin organization and genomic interactions at sub-kilobase-pair resolution that requires minimal cell numbers and sequencing depth.

    • Petros Kolovos
    • , Rutger W W Brouwer
    • , Christel E M Kockx
    • , Michael Lesnussa
    • , Nick Kepper
    • , Jessica Zuin
    • , A M Ali Imam
    • , Harmen J G van de Werken
    • , Kerstin S Wendt
    • , Tobias A Knoch
    • , Wilfred F J van IJcken
    •  &  Frank Grosveld
  • Nature Protocols | Protocol

    This protocol describes how to prepare samples for labeling nuclei of cultured mammalian cells for 3D structured illumination microscopy of nuclear structures. Image acquisition, registration and downstream image analysis are also described.

    • Felix Kraus
    • , Ezequiel Miron
    • , Justin Demmerle
    • , Tsotne Chitiashvili
    • , Alexei Budco
    • , Quentin Alle
    • , Atsushi Matsuda
    • , Heinrich Leonhardt
    • , Lothar Schermelleh
    •  &  Yolanda Markaki
  • Nature Protocols | Protocol

    Li et al. provide a protocol for long-read ChIA-PET, a technique for mapping chromatin interactions. The longer paired-end tags, which are generated by tagmentation, provide sufficient coverage to determine haplotype-specific chromatin interactions at single-nucleotide resolution.

    • Xingwang Li
    • , Oscar Junhong Luo
    • , Ping Wang
    • , Meizhen Zheng
    • , Danjuan Wang
    • , Emaly Piecuch
    • , Jacqueline Jufen Zhu
    • , Simon Zhongyuan Tian
    • , Zhonghui Tang
    • , Guoliang Li
    •  &  Yijun Ruan
  • Nature Protocols | Protocol

    Ramani et al. describe a protocol for in situ DNase Hi-C as an alternative to traditional Hi-C methods that use restriction enzymes. The use of DNase I for chromatin digestion circumvents the resolution limit imposed when relying on genomic restriction sites.

    • Vijay Ramani
    • , Darren A Cusanovich
    • , Ronald J Hause
    • , Wenxiu Ma
    • , Ruolan Qiu
    • , Xinxian Deng
    • , C Anthony Blau
    • , Christine M Disteche
    • , William S Noble
    • , Jay Shendure
    •  &  Zhijun Duan