An integrated view of the structure and function of the human 4D nucleome
Abstract
Abstract The dynamic three-dimensional (3D) organization of the human genome (the 4D nucleome) is linked to genome function. Here we describe efforts by the 4D Nucleome Project 1 to map and analyse the 4D nucleome in widely used H1 human embryonic stem cells and immortalized fibroblasts (HFFc6). We produced and integrated diverse genomic datasets of the 4D nucleome, each contributing unique observations, which enabled us to assemble extensive catalogues of more than 140,000 looping interactions per cell type, to generate detailed classifications and annotations of chromosomal domain types and their subnuclear positions, and to obtain single-cell 3D models of the nuclear environment of all genes including their long-range interactions with distal elements. Through extensive benchmarking, we describe the unique strengths of different genomic assays for studying the 4D nucleome, providing guidelines for future studies. Three-dimensional models of population-based and individual cell-to-cell variation in genome structure showed connections between chromosome folding, nuclear organization, chromatin looping, gene transcription and DNA replication. Finally, we demonstrate the use of computational methods to predict genome folding from DNA sequence, which will facilitate the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.
Article Details
Authors (90)
Job Dekker
Betul Akgol Oksuz
Yang Zhang
Ye Wang
Miriam K. Minsk
Shuzhen Kuang
Liyan Yang
Johan H. Gibcus
Nils Krietenstein
Oliver J. Rando
Jie Xu
Derek H. Janssens
Steven Henikoff
Alexander Kukalev
Willemin Andréa
Warren Winick-Ng
Rieke Kempfer
Ana Pombo
Miao Yu
Pradeep Kumar
Liguo Zhang
Andrew S. Belmont
Takayo Sasaki
Tom van Schaik
Laura Brueckner
Daan Peric-Hupkes
Bas van Steensel
Ping Wang
Haoxi Chai
Minji Kim
Yijun Ruan
Ran Zhang
Sofia A. Quinodoz
Prashant Bhat
Mitchell Guttman
Wenxin Zhao
Shu Chien
Yuan Liu
Sergey V. Venev
Dariusz Plewczynski
Ibai Irastorza Azcarate
Dominik Szabó
Christoph J. Thieme
Teresa Szczepińska
Mateusz Chiliński
Kaustav Sengupta
Mattia Conte
Andrea Esposito
Alex Abraham
Ruochi Zhang
Yuchuan Wang
Xingzhao Wen
Qiuyang Wu
Yang Yang
Jie Liu
Lorenzo Boninsegna
Asli Yildirim
Yuxiang Zhan
Andrea Maria Chiariello
Simona Bianco
Lindsay Lee
Ming Hu
Yun Li
R. Jordan Barnett
Ashley L. Cook
Daniel J. Emerson
Claire Marchal
Peiyao Zhao
Peter J. Park
Burak H. Alver
Andrew J. Schroeder
Rahi Navelkar
Clara Bakker
William Ronchetti
Shannon Ehmsen
Alexander D. Veit
Nils Gehlenborg
Ting Wang
Department of Radiation Oncology The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital Zhengzhou China
Daofeng Li
Xiaotao Wang
Mario Nicodemi
Bing Ren
Sheng Zhong
Jennifer E. Phillips-Cremins
David M. Gilbert
Katherine S. Pollard
Frank Alber
Jian Ma
William S. Noble
Feng Yue