The 4D nucleome project

The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions. The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions. Validated experimental technologies will be combined with biophysical approaches to generate quantitative models of spatial genome organization in different biological states, both in cell populations and in single cells.

[1]  Mark H. Ellisman,et al.  Serial Section Electron Tomography: A Method for Three-Dimensional Reconstruction of Large Structures , 1994, NeuroImage.

[2]  A S Belmont,et al.  In vivo localization of DNA sequences and visualization of large-scale chromatin organization using lac operator/repressor recognition , 1996, The Journal of cell biology.

[3]  G. Sallit.  Beyond Pretty Pictures , 1997 .

[4]  S. Henikoff,et al.  Identification of in vivo DNA targets of chromatin proteins using tethered Dam methyltransferase , 2000, Nature Biotechnology.

[5]  T. Cremer,et al.  Chromosome territories, nuclear architecture and gene regulation in mammalian cells , 2001, Nature Reviews Genetics.

[6]  J. Dekker,et al.  Capturing Chromosome Conformation , 2002, Science.

[7]  Erik Splinter,et al.  Looping and interaction between hypersensitive sites in the active beta-globin locus. , 2002, Molecular cell.

[8]  J. Marko,et al.  Micromechanical studies of mitotic chromosomes. , 2002, Journal of muscle research and cell motility.

[9]  Tom Misteli,et al.  Spatial proximity of translocation-prone gene loci in human lymphomas , 2003, Nature Genetics.

[10]  S. Salzberg,et al.  The Transcriptional Landscape of the Mammalian Genome , 2005, Science.

[11]  J. Lippincott-Schwartz,et al.  Imaging Intracellular Fluorescent Proteins at Nanometer Resolution , 2006, Science.

[12]  Michael D. Mason,et al.  Ultra-high resolution imaging by fluorescence photoactivation localization microscopy. , 2006, Biophysical journal.

[13]  C. Nusbaum,et al.  Chromosome Conformation Capture Carbon Copy (5C): a massively parallel solution for mapping interactions between genomic elements. , 2006, Genome research.

[14]  Konstantin A Lukyanov,et al.  A genetically encoded photosensitizer , 2006, Nature Biotechnology.

[15]  Michael J Rust,et al.  Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM) , 2006, Nature Methods.

[16]  B. Steensel,et al.  Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture–on-chip (4C) , 2006, Nature Genetics.

[17]  Wouter de Laat,et al.  Quantitative analysis of chromosome conformation capture assays (3C-qPCR) , 2007, Nature Protocols.

[18]  Bas van Steensel,et al.  Detection of in vivo protein–DNA interactions using DamID in mammalian cells , 2007, Nature Protocols.

[19]  L. Wessels,et al.  Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions , 2008, Nature.

[20]  Dirk Schübeler,et al.  Global Reorganization of Replication Domains During Embryonic Stem Cell Differentiation , 2008, PLoS biology.

[21]  Roel van Driel,et al.  Studying physical chromatin interactions in plants using Chromosome Conformation Capture (3C) , 2009, Nature Protocols.

[22]  E. Liu,et al.  An Oestrogen Receptor α-bound Human Chromatin Interactome , 2009, Nature.

[23]  I. Amit,et al.  Comprehensive mapping of long range interactions reveals folding principles of the human genome , 2011 .

[24]  B. Jones,et al.  Global identification of yeast chromosome interactions using Genome conformation capture. , 2009, Fungal genetics and biology : FG & B.

[25]  Michael O Dorschner,et al.  Sequencing newly replicated DNA reveals widespread plasticity in human replication timing , 2009, Proceedings of the National Academy of Sciences.

[26]  L. Schermelleh,et al.  Functional nuclear organization of transcription and DNA replication: a topographical marriage between chromatin domains and the interchromatin compartment. , 2010, Cold Spring Harbor symposia on quantitative biology.

[27]  A. Lamond,et al.  High-Resolution Whole-Genome Sequencing Reveals That Specific Chromatin Domains from Most Human Chromosomes Associate with Nucleoli , 2010, Molecular biology of the cell.

[28]  A. Conesa,et al.  Initial Genomics of the Human Nucleolus , 2010, PLoS genetics.

[29]  Marc A. Martí-Renom,et al.  Bridging the Resolution Gap in Structural Modeling of 3D Genome Organization , 2011, PLoS Comput. Biol..

[30]  Brad A Chapman,et al.  The genomic binding sites of a noncoding RNA , 2011, Proceedings of the National Academy of Sciences.

[31]  Tyrone Ryba,et al.  Genome-scale analysis of replication timing: from bench to bioinformatics , 2011, Nature Protocols.

[32]  Bin Zhang,et al.  Biogenesis and function of nuclear bodies. , 2011, Trends in genetics : TIG.

[33]  Elzo de Wit,et al.  4C technology: protocols and data analysis. , 2012, Methods in enzymology.

[34]  Mark H. Ellisman,et al.  Engineered ascorbate peroxidase as a genetically-encoded reporter for electron microscopy , 2012, Nature Biotechnology.

[35]  Elzo de Wit,et al.  Determining long-range chromatin interactions for selected genomic sites using 4C-seq technology: from fixation to computation. , 2012, Methods.

[36]  M. Dundr,et al.  Nuclear bodies: multifunctional companions of the genome. , 2012, Current opinion in cell biology.

[37]  Job Dekker,et al.  Analysis of long-range chromatin interactions using Chromosome Conformation Capture. , 2012, Methods.

[38]  Reza Kalhor,et al.  Genome architectures revealed by tethered chromosome conformation capture and population-based modeling , 2011, Nature Biotechnology.

[39]  J. Sedat,et al.  Spatial partitioning of the regulatory landscape of the X-inactivation centre , 2012, Nature.

[40]  Shane J. Neph,et al.  Systematic Localization of Common Disease-Associated Variation in Regulatory DNA , 2012, Science.

[41]  Ignacio Izeddin,et al.  PSF shaping using adaptive optics for three-dimensional single-molecule super-resolution imaging and tracking. , 2012, Optics express.

[42]  Jesse R. Dixon,et al.  Topological Domains in Mammalian Genomes Identified by Analysis of Chromatin Interactions , 2012, Nature.

[43]  Michael S. Becker,et al.  Spatial Organization of the Mouse Genome and Its Role in Recurrent Chromosomal Translocations , 2012, Cell.

[44]  Matthew J. Paszek,et al.  Scanning Angle Interference Microscopy Reveals Cell Dynamics at the Nano-scale , 2012, Nature Methods.

[45]  Robert H Singer,et al.  Single-molecule analysis of gene expression using two-color RNA labeling in live yeast , 2012, Nature Methods.

[46]  Wouter Meuleman,et al.  Chromatin Position Effects Assayed by Thousands of Reporters Integrated in Parallel , 2013, Cell.

[47]  A. Tanay,et al.  Single cell Hi-C reveals cell-to-cell variability in chromosome structure , 2013, Nature.

[48]  N. Daigle,et al.  Nuclear Pore Scaffold Structure Analyzed by Super-Resolution Microscopy and Particle Averaging , 2013, Science.

[49]  E. Lander,et al.  The Xist lncRNA Exploits Three-Dimensional Genome Architecture to Spread Across the X Chromosome , 2013, Science.

[50]  Yusuke Miyanari,et al.  Live visualization of chromatin dynamics with fluorescent TALEs , 2013, Nature Structural &Molecular Biology.

[51]  Wendy A Bickmore,et al.  The spatial organization of the human genome. , 2013, Annual review of genomics and human genetics.

[52]  Ignacio Izeddin,et al.  Real-Time Dynamics of RNA Polymerase II Clustering in Live Human Cells , 2013, Science.

[53]  Job Dekker,et al.  Organization of the Mitotic Chromosome , 2013, Science.

[54]  Thoru Pederson,et al.  Visualization of repetitive DNA sequences in human chromosomes with transcription activator-like effectors , 2013, Proceedings of the National Academy of Sciences.

[55]  M. Groudine,et al.  Nucleolar tethering mediates pairing between the IgH and Myc loci , 2014, Nucleus.

[56]  Ludo Pagie,et al.  Using TRIP for genome-wide position effect analysis in cultured cells , 2014, Nature Protocols.

[57]  Yaojun Zhang,et al.  3D Trajectories Adopted by Coding and Regulatory DNA Elements: First-Passage Times for Genomic Interactions , 2014, Cell.

[58]  A. Ashworth,et al.  Unbiased analysis of potential targets of breast cancer susceptibility loci by Capture Hi-C , 2014, Genome research.

[59]  Wei Zhang,et al.  Dynamic Imaging of Genomic Loci in Living Human Cells by an Optimized CRISPR/Cas System , 2014, Cell.

[60]  Philip D. Gregory,et al.  Reactivation of Developmentally Silenced Globin Genes by Forced Chromatin Looping , 2014, Cell.

[61]  Elizabeth A. Smith,et al.  Quantitatively imaging chromosomes by correlated cryo-fluorescence and soft x-ray tomographies. , 2014, Biophysical journal.

[62]  Sharon R Grossman,et al.  RNA-RNA Interactions Enable Specific Targeting of Noncoding RNAs to Nascent Pre-mRNAs and Chromatin Sites , 2014, Cell.

[63]  M. Dahan,et al.  Single-molecule tracking in live cells reveals distinct target-search strategies of transcription factors in the nucleus , 2014, eLife.

[64]  Wesley R. Legant,et al.  Single-Molecule Dynamics of Enhanceosome Assembly in Embryonic Stem Cells , 2014, Cell.

[65]  M. Gobbi,et al.  Analysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experiment , 2014, Nature Genetics.

[66]  Mario Nicodemi,et al.  Physical mechanisms behind the large scale features of chromatin organization. , 2014, Transcription.

[67]  Yanli Wang,et al.  Topologically associating domains are stable units of replication-timing regulation , 2014, Nature.

[68]  Daniel Jost,et al.  Modeling epigenome folding: formation and dynamics of topologically associated chromatin domains , 2014, Nucleic acids research.

[69]  Wesley R. Legant,et al.  Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution , 2014, Science.

[70]  Timur Zhiyentayev,et al.  Single-cell in situ RNA profiling by sequential hybridization , 2014, Nature Methods.

[71]  Neva C. Durand,et al.  A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping , 2014, Cell.

[72]  Peter H. L. Krijger,et al.  CTCF Binding Polarity Determines Chromatin Looping. , 2015, Molecular cell.

[73]  Robert Tjian,et al.  CASFISH: CRISPR/Cas9-mediated in situ labeling of genomic loci in fixed cells , 2015, Proceedings of the National Academy of Sciences.

[74]  Shaojie Zhang,et al.  Multicolor CRISPR labeling of chromosomal loci in human cells , 2015, Proceedings of the National Academy of Sciences.

[75]  D. Gallie.  Faculty Opinions recommendation of The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3. , 2015 .

[76]  William Stafford Noble,et al.  Fine-scale chromatin interaction maps reveal the cis-regulatory landscape of human lincRNA genes , 2014, Nature Methods.

[77]  Jing Liang,et al.  Chromatin architecture reorganization during stem cell differentiation , 2015, Nature.

[78]  Nir Friedman,et al.  Mapping Nucleosome Resolution Chromosome Folding in Yeast by Micro-C , 2015, Cell.

[79]  Sigal Shachar,et al.  Identification of Gene Positioning Factors Using High-Throughput Imaging Mapping , 2015, Cell.

[80]  D. Odom,et al.  Comparative Hi-C Reveals that CTCF Underlies Evolution of Chromosomal Domain Architecture , 2015, Cell reports.

[81]  Qiangfeng Cliff Zhang,et al.  Systematic Discovery of Xist RNA Binding Proteins , 2015, Cell.

[82]  Dariusz M Plewczynski,et al.  CTCF-Mediated Human 3D Genome Architecture Reveals Chromatin Topology for Transcription , 2015, Cell.

[83]  J. J. Macklin,et al.  A general method to improve fluorophores for live-cell and single-molecule microscopy , 2014, Nature Methods.

[84]  Geoffrey Fudenberg,et al.  Modeling chromosomes: Beyond pretty pictures , 2015, FEBS letters.

[85]  Neva C. Durand,et al.  Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes , 2015, Proceedings of the National Academy of Sciences.

[86]  Siddharth S. Dey,et al.  Genome-wide Maps of Nuclear Lamina Interactions in Single Human Cells , 2015, Cell.

[87]  Yannick G. Spill,et al.  Restraint‐based three‐dimensional modeling of genomes and genomic domains , 2015, FEBS letters.

[88]  Michael Q. Zhang,et al.  Integrative analysis of 111 reference human epigenomes , 2015, Nature.

[89]  Neva C. Durand,et al.  Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture , 2016, Proceedings of the National Academy of Sciences.

[90]  Howard Y. Chang,et al.  Structural organization of the inactive X chromosome in the mouse , 2016, Nature.

[91]  L. Mirny,et al.  Formation of Chromosomal Domains in Interphase by Loop Extrusion , 2015, bioRxiv.

[92]  Shaojie Zhang,et al.  CRISPR-Cas9 nuclear dynamics and target recognition in living cells , 2016, The Journal of cell biology.

[93]  Shaojie Zhang,et al.  Multiplexed labeling of genomic loci with dCas9 and engineered sgRNAs using CRISPRainbow , 2016, Nature Biotechnology.

[94]  Ludo Pagie,et al.  Inducible DamID systems for genomic mapping of chromatin proteins in Drosophila , 2016, Nucleic acids research.

[95]  Wendell A Lim,et al.  CRISPR/Cas9 for Human Genome Engineering and Disease Research. , 2016, Annual review of genomics and human genetics.

[96]  Wouter de Laat,et al.  The second decade of 3C technologies: detailed insights into nuclear organization , 2016, Genes & development.

[97]  Lei S. Qi,et al.  CRISPR/Cas9 in Genome Editing and Beyond. , 2016, Annual review of biochemistry.

[98]  Xiaohua Wan,et al.  3D reconstruction of biological structures: automated procedures for alignment and reconstruction of multiple tilt series in electron tomography , 2016, Advanced Structural and Chemical Imaging.

[99]  Steven J. M. Jones,et al.  The International Human Epigenome Consortium: A Blueprint for Scientific Collaboration and Discovery , 2016, Cell.

[100]  G. Fudenberg,et al.  FISH-ing for captured contacts: towards reconciling FISH and 3C , 2016, bioRxiv.

[101]  Michael Levine,et al.  Enhancer Control of Transcriptional Bursting , 2016, Cell.

[102]  Jesse M. Engreitz,et al.  Long non-coding RNAs: spatial amplifiers that control nuclear structure and gene expression , 2016, Nature Reviews Molecular Cell Biology.

[103]  Geoffrey Fudenberg,et al.  Micro-C XL: assaying chromosome conformation from the nucleosome to the entire genome , 2016, Nature Methods.

[104]  L. Mirny,et al.  The 3D Genome as Moderator of Chromosomal Communication , 2016, Cell.

[105]  Wesley R. Legant,et al.  High density three-dimensional localization microscopy across large volumes , 2016, Nature Methods.

[106]  Mark Groudine,et al.  The redundancy of the mammalian heterochromatic compartment. , 2016, Current opinion in genetics & development.

[107]  Mason R. Mackey,et al.  Multicolor Electron Microscopy for Simultaneous Visualization of Multiple Molecular Species. , 2016, Cell chemical biology.

[108]  Manolis Kellis,et al.  Soft X-Ray Tomography Reveals Gradual Chromatin Compaction and Reorganization during Neurogenesis In Vivo. , 2016, Cell reports.

[109]  Geunsik Lee,et al.  APEX Fingerprinting Reveals the Subcellular Localization of Proteins of Interest. , 2016, Cell reports.

[110]  Edith Heard,et al.  Closing the loop: 3C versus DNA FISH , 2016, Genome Biology.

[111]  R. Tjian,et al.  CTCF and cohesin regulate chromatin loop stability with distinct dynamics , 2016, bioRxiv.

[112]  Sébastien Phan,et al.  ChromEMT: Visualizing 3D chromatin structure and compaction in interphase and mitotic cells , 2017, Science.

[113]  Thomas Gregor,et al.  Direct visualization of transcriptional activation by physical enhancer–promoter proximity , 2017, bioRxiv.

[114]  R. Ghosh,et al.  A fluorogenic nanobody array tag for prolonged single molecule imaging in live cells , 2017, bioRxiv.

[115]  Lei S. Qi,et al.  Multiplexed Dynamic Imaging of Genomic Loci by Combined CRISPR Imaging and DNA Sequential FISH , 2017, Biophysical journal.

[116]  William Stafford Noble,et al.  Massively multiplex single-cell Hi-C , 2016, Nature Methods.

[117]  S. Q. Xie,et al.  Complex multi-enhancer contacts captured by Genome Architecture Mapping (GAM) , 2017, Nature.

[118]  Frank Alber,et al.  Comprehensive characterization of neutrophil genome topology , 2017, bioRxiv.