The 4D nucleome: Evidence for a dynamic nuclear landscape based on co‐aligned active and inactive nuclear compartments

Recent methodological advancements in microscopy and DNA sequencing‐based methods provide unprecedented new insights into the spatio‐temporal relationships between chromatin and nuclear machineries. We discuss a model of the underlying functional nuclear organization derived mostly from electron and super‐resolved fluorescence microscopy studies. It is based on two spatially co‐aligned, active and inactive nuclear compartments (ANC and INC). The INC comprises the compact, transcriptionally inactive core of chromatin domain clusters (CDCs). The ANC is formed by the transcriptionally active periphery of CDCs, called the perichromatin region (PR), and the interchromatin compartment (IC). The IC is connected to nuclear pores and serves nuclear import and export functions. The ANC is the major site of RNA synthesis. It is highly enriched in epigenetic marks for transcriptionally competent chromatin and RNA Polymerase II. Marks for silent chromatin are enriched in the INC. Multi‐scale cross‐correlation spectroscopy suggests that nuclear architecture resembles a random obstacle network for diffusing proteins. An increased dwell time of proteins and protein complexes within the ANC may help to limit genome scanning by factors or factor complexes to DNA exposed within the ANC.

[1]  G. Schroth,et al.  Cohesin-mediated interactions organize chromosomal domain architecture , 2013, The EMBO journal.

[2]  Hans-Jörg Rheinberger,et al.  Thomas Cremer: Von der Zellenlehre zur Chromosomentheorie. Naturwissenschaftliche Erkenntnis und Theorienwechsel in der frühen Zell- und Vererbungsforschung. Berlin-Heidelberg-New York-Tokyo: Springer-Verlag 1985. XVI + 384 Seiten, DM 135,-. , 1987 .

[3]  Theodor Boveri,et al.  Die Blastomerenkerne von Ascaris Megalocephala und die Theorie der Chromosomenindividualität , 1909 .

[4]  L. Hnilica.  Proteins of the Cell Nucleus , 1967 .

[5]  Thomas Cremer,et al.  Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci , 2014, Epigenetics & Chromatin.

[6]  Thomas Cremer,et al.  4D Chromatin dynamics in cycling cells , 2010 .

[7]  Dieter W. Heermann,et al.  Diffusion-Driven Looping Provides a Consistent Framework for Chromatin Organization , 2010, PloS one.

[8]  J. E. Mazur,et al.  Half a century. , 2008, Journal of the experimental analysis of behavior.

[9]  S. Razin,et al.  The channels model of nuclear matrix structure , 1995, BioEssays : news and reviews in molecular, cellular and developmental biology.

[10]  P. Lichter,et al.  Diffusion-limited compartmentalization of mammalian cell nuclei assessed by microinjected macromolecules. , 2003, Experimental cell research.

[11]  V. Corces,et al.  CTCF: an architectural protein bridging genome topology and function , 2014, Nature Reviews Genetics.

[12]  Yi Zhang,et al.  TET enzymes, TDG and the dynamics of DNA demethylation , 2013, Nature.

[13]  Filipa L. Sousa,et al.  Origins of major archaeal clades correspond to gene acquisitions from bacteria , 2014, Nature.

[14]  Ernst H. K. Stelzer.  Better Imaging through Chemistry , 2014, Cell.

[15]  P. Lichter,et al.  Histone acetylation increases chromatin accessibility , 2005, Journal of Cell Science.

[16]  Thomas Cremer,et al.  4D chromatin dynamics in cycling cells: Theodor Boveri's hypotheses revisited. , 2010, Nucleus.

[17]  P. Lichter,et al.  Recollections of a scientific journey published in human genetics: from chromosome territories to interphase cytogenetics and comparative genome hybridization , 2014, Human Genetics.

[18]  K. Maeshima,et al.  Chromatin as dynamic 10-nm fibers , 2014, Chromosoma.

[19]  Kazuhiro Maeshima,et al.  Chromatin structure: does the 30-nm fibre exist in vivo? , 2010, Current opinion in cell biology.

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

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

[22]  H. Zentgraf,et al.  Characterization and localization of the RNA synthesized in mature avian erythrocytes. , 1975, Experimental cell research.

[23]  Mike Heilemann,et al.  Super-resolution fluorescence imaging of chromosomal DNA. , 2012, Journal of structural biology.

[24]  Ernst H. K. Stelzer,et al.  Structure and dynamics of human interphase chromosome territories in vivo , 1998, Human Genetics.

[25]  Thomas Cremer,et al.  The potential of 3D‐FISH and super‐resolution structured illumination microscopy for studies of 3D nuclear architecture , 2012, BioEssays : news and reviews in molecular, cellular and developmental biology.

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

[27]  T. Misteli,et al.  Activation of DNA damage response signaling by condensed chromatin. , 2014, Cell reports.

[28]  Michael J. Zeitz,et al.  Matrin 3: Chromosomal distribution and protein interactions , 2009, Journal of cellular biochemistry.

[29]  Y. Vassetzky,et al.  Nuclear matrix and structural and functional compartmentalization of the eucaryotic cell nucleus , 2014, Biochemistry (Moscow).

[30]  Yiider Tseng,et al.  Micro-organization and visco-elasticity of the interphase nucleus revealed by particle nanotracking , 2004, Journal of Cell Science.

[31]  E. Weiss,et al.  Live cell immunogold labelling of RNA polymerase II , 2015, Scientific Reports.

[32]  C. Lanctôt,et al.  The International Nucleome Consortium , 2015, Nucleus.

[33]  P. Lichter,et al.  Evidence for a nuclear compartment of transcription and splicing located at chromosome domain boundaries , 1993, Chromosome Research.

[34]  M. Renz.  Fluorescence microscopy—A historical and technical perspective , 2013, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[35]  S. Rehbein,et al.  Multimodal nanoparticles as alignment and correlation markers in fluorescence/soft X-ray cryo-microscopy/tomography of nucleoplasmic reticulum and apoptosis in mammalian cells , 2014, Ultramicroscopy.

[36]  A. Sandberg,et al.  Chromosomes and their relationship to nuclear components during the cell cycle in Chinese hamster cells , 2004, Cell and Tissue Research.

[37]  Thomas Cremer,et al.  Revealing the high-resolution three-dimensional network of chromatin and interchromatin space: A novel electron-microscopic approach to reconstructing nuclear architecture , 2009, Chromosome Research.

[38]  D. E. Olins,et al.  Retrotransposon Alu is enriched in the epichromatin of HL-60 cells , 2014, Nucleus.

[39]  Mario Nicodemi,et al.  Complexity of chromatin folding is captured by the strings and binders switch model , 2012, Proceedings of the National Academy of Sciences.

[40]  Heinrich Leonhardt,et al.  Visualization of specific DNA sequences in living mouse embryonic stem cells with a programmable fluorescent CRISPR/Cas system , 2014, Nucleus.

[41]  Thomas Cremer,et al.  Rise, fall and resurrection of chromosome territories: a historical perspective. Part I. The rise of chromosome territories. , 2006, European journal of histochemistry : EJH.

[42]  J. Aten,et al.  Fine structural in situ analysis of nascent DNA movement following DNA replication. , 2000, Experimental cell research.

[43]  Thomas Cremer,et al.  Nuclear Architecture of Rod Photoreceptor Cells Adapts to Vision in Mammalian Evolution , 2009, Cell.

[44]  S. Fakan,et al.  Localisation of rapidly and slowly labelled nuclear RNA as visualized by high resolution autoradiography. , 1971, Experimental cell research.

[45]  T. Cremer,et al.  Evolutionary origin of the cell nucleus and its functional architecture. , 2010, Essays in biochemistry.

[46]  S. Razin,et al.  A requiem to the nuclear matrix: from a controversial concept to 3D organization of the nucleus , 2014, Chromosoma.

[47]  J. Dekker,et al.  The hierarchy of the 3D genome. , 2013, Molecular cell.

[48]  Elizabeth A. Smith,et al.  Correlative microscopy methods that maximize specimen fidelity and data completeness, and improve molecular localization capabilities. , 2013, Journal of structural biology.

[49]  A. Monneron,et al.  Fine structural organization of the interphase nucleus in some mammalian cells. , 1969, Journal of ultrastructure research.

[50]  T. Cremer,et al.  Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions , 2007, Nature Reviews Genetics.

[51]  Ronald Berezney,et al.  Spatial and Temporal Dynamics of DNA Replication Sites in Mammalian Cells , 1998, The Journal of cell biology.

[52]  W. Doolittle,et al.  Eukaryogenesis, how special really? , 2015, Proceedings of the National Academy of Sciences.

[53]  Roel van Driel,et al.  Depletion of the Chromatin Looping Proteins CTCF and Cohesin Causes Chromatin Compaction: Insight into Chromatin Folding by Polymer Modelling , 2014, PLoS Comput. Biol..

[54]  K. Rippe,et al.  Nuclear architecture by RNA. , 2012, Current opinion in genetics & development.

[55]  John Bechhoefer,et al.  What is superresolution microscopy , 2014, 1405.1118.

[56]  W. Bickmore,et al.  Single-Cell Dynamics of Genome-Nuclear Lamina Interactions , 2013, Cell.

[57]  F. Grosveld,et al.  Transcription in the context of the 3D nucleus. , 2014, Current opinion in genetics & development.

[58]  R. Eils,et al.  4-D single particle tracking of synthetic and proteinaceous microspheres reveals preferential movement of nuclear particles along chromatin – poor tracks , 2004, BMC Cell Biology.

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

[60]  R. Hancock,et al.  Preface. New models of the cell nucleus: crowding, entropic forces, phase separation, and fractals. , 2014, International review of cell and molecular biology.

[61]  J O Bustamante,et al.  Electrical dimension of the nuclear envelope. , 2001, Physiological reviews.

[62]  G. Blobel,et al.  Gene gating: a hypothesis. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[63]  T. Cremer,et al.  Centennial of Wilhelm Waldeyer's introduction of the term "chromosome" in 1888. , 1988, Cytogenetics and cell genetics.

[64]  S. Gasser,et al.  INO80 and SWR complexes: relating structure to function in chromatin remodeling. , 2014, Trends in cell biology.

[65]  P. Flicek,et al.  Molecular maps of the reorganization of genome-nuclear lamina interactions during differentiation. , 2010, Molecular cell.

[66]  Andrey G. Cherstvy,et al.  Structure-driven homology pairing of chromatin fibers: the role of electrostatics and protein-induced bridging , 2013, Journal of Biological Physics.

[67]  M. G. Kidwell,et al.  PERSPECTIVE: TRANSPOSABLE ELEMENTS, PARASITIC DNA, AND GENOME EVOLUTION , 2001, Evolution; international journal of organic evolution.

[68]  Thomas Cremer,et al.  Von der Zellenlehre zur Chromosomentheorie : naturwissenschaftliche Erkenntnis und Theorienwechsel in der frühen Zell- und Vererbungsforschung , 1985 .

[69]  Achilleas S Frangakis,et al.  Analysis of cryo-electron microscopy images does not support the existence of 30-nm chromatin fibers in mitotic chromosomes in situ , 2008, Proceedings of the National Academy of Sciences.

[70]  Y. Shav-Tal,et al.  Dynamics of single mRNP nucleocytoplasmic transport and export through the nuclear pore in living cells , 2010, Nature Cell Biology.

[71]  A. Belmont,et al.  HSP70 Transgene Directed Motion to Nuclear Speckles Facilitates Heat Shock Activation , 2014, Current Biology.

[72]  Chao Zhou,et al.  Fluorescence and SEM correlative microscopy for nanomanipulation of subcellular structures , 2014 .

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

[74]  Michael Hausmann,et al.  Combinatorial selection of short triplex forming oligonucleotides for fluorescence in situ hybridisation COMBO-FISH , 2012, J. Comput. Sci..

[75]  K. Kalland,et al.  Transcribed DNA is preferentially located in the perichromatin region of mammalian cell nuclei. , 2011, Experimental cell research.

[76]  M. Durante,et al.  Species conserved DNA damage response at the inactive human X chromosome. , 2013, Mutation research.

[77]  Barry R. Masters,et al.  Resolution enhancement techniques in microscopy , 2013 .

[78]  E. P. Tinnel,et al.  Electron microscope tomography: transcription in three dimensions. , 1983, Science.

[79]  T. Pederson.  The nuclear physique. , 2014, International review of cell and molecular biology.

[80]  F. Pérez-Willard,et al.  Focused ion beam (FIB) combined with high resolution scanning electron microscopy: a promising tool for 3D analysis of chromosome architecture. , 2009, Journal of structural biology.

[81]  S. Hopper.  Royal Botanic Gardens Kew , 2015 .

[82]  Yoshinori Nishino,et al.  Chromosomes without a 30-nm chromatin fiber , 2012, Nucleus.

[83]  Raoul Kopelman,et al.  "Nanosized voltmeter" enables cellular-wide electric field mapping. , 2007, Biophysical journal.

[84]  P. Schultz,et al.  In Vivo Chromatin Organization of Mouse Rod Photoreceptors Correlates with Histone Modifications , 2010, PloS one.

[85]  Heinrich Leonhardt,et al.  Targeting and tracing of specific DNA sequences with dTALEs in living cells , 2013, Nucleic acids research.

[86]  T. Cremer,et al.  Chromosome territories. , 2010, Cold Spring Harbor perspectives in biology.

[87]  K. Smetana,et al.  A CONTRIBUTION TO THE KNOWLEDGE OF THE ULTRASTRUCTURE OF LEUKAEMIC LYMPHOCYTES. , 1963, Neoplasma.

[88]  M. Ramalho-Santos,et al.  Open chromatin in pluripotency and reprogramming , 2010, Nature Reviews Molecular Cell Biology.

[89]  L. Mirny,et al.  Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data , 2013, Nature Reviews Genetics.

[90]  Thomas Cremer,et al.  Functional nuclear architecture studied by microscopy: present and future. , 2010, International review of cell and molecular biology.

[91]  J. Dekker,et al.  Predictive Polymer Modeling Reveals Coupled Fluctuations in Chromosome Conformation and Transcription , 2014, Cell.

[92]  R. van Driel,et al.  Ultrastructural analysis of transcription and splicing in the cell nucleus after bromo-UTP microinjection. , 1999, Molecular biology of the cell.

[93]  Mario Nicodemi,et al.  Models of chromosome structure. , 2014, Current opinion in cell biology.

[94]  Robert S. Illingworth,et al.  Chromatin decondensation is sufficient to alter nuclear organization in embryonic stem cells , 2014, Science.

[95]  R. Hancock,et al.  Internal organisation of the nucleus: assembly of compartments by macromolecular crowding and the nuclear matrix model , 2004, Biology of the cell.

[96]  M. Bustin,et al.  Distinct Properties of Human HMGN5 Reveal a Rapidly Evolving but Functionally Conserved Nucleosome Binding Protein , 2011, Molecular and Cellular Biology.

[97]  Volker J Schmid,et al.  Reprogramming of fibroblast nuclei in cloned bovine embryos involves major structural remodeling with both striking similarities and differences to nuclear phenotypes of in vitro fertilized embryos , 2014, Nucleus.

[98]  Mark Groudine,et al.  Form follows function: The genomic organization of cellular differentiation. , 2004, Genes & development.

[99]  T. Cremer,et al.  Competition effect in DNA damage response , 2008, Radiation and environmental biophysics.

[100]  G. Schotta,et al.  Specificity, propagation, and memory of pericentric heterochromatin , 2014, Molecular systems biology.

[101]  Kurt Kremer,et al.  From a melt of rings to chromosome territories: the role of topological constraints in genome folding , 2013, Reports on progress in physics. Physical Society.

[102]  T. Gregory,et al.  The Case for Junk DNA , 2014, PLoS genetics.

[103]  Volker J Schmid,et al.  Double-strand break-induced transcriptional silencing is associated with loss of tri-methylation at H3K4 , 2011, Chromosome Research.

[104]  T. Cremer,et al.  Chromosome territories, nuclear matrix filaments and inter-chromatin channels: a topological view on nuclear architecture and function , 2005 .

[105]  M. Baum,et al.  The viscoelastic properties of chromatin and the nucleoplasm revealed by scale-dependent protein mobility , 2014, Journal of physics. Condensed matter : an Institute of Physics journal.

[106]  K. Buetow,et al.  Allelic variation in gene expression is common in the human genome. , 2003, Genome research.

[107]  T. Misteli,et al.  Spatial Dynamics of Chromosome Translocations in Living Cells , 2013, Science.

[108]  J A Aten,et al.  RNA polymerase II transcription is concentrated outside replication domains throughout S-phase. , 1994, Journal of cell science.

[109]  B. Frieden,et al.  Intracellular Electric Field and pH Optimize Protein Localization and Movement , 2012, PloS one.

[110]  S. Razin,et al.  Specificity and functional significance of DNA interaction with the nuclear matrix: new approaches to clarify the old questions. , 1995, International review of cytology.

[111]  T. Cremer,et al.  Recruitment Kinetics of DNA Repair Proteins Mdc1 and Rad52 but Not 53BP1 Depend on Damage Complexity , 2012, PloS one.

[112]  Giacomo Cavalli,et al.  The Role of Chromosome Domains in Shaping the Functional Genome , 2015, Cell.

[113]  S. Cockroft,et al.  Transcription forms and remodels supercoiling domains unfolding large-scale chromatin structures , 2013, Nature Structural &Molecular Biology.

[114]  S. Ohno,et al.  So much "junk" DNA in our genome. , 1972, Brookhaven symposia in biology.

[115]  C Cremer,et al.  Role of chromosome territories in the functional compartmentalization of the cell nucleus. , 1993, Cold Spring Harbor symposia on quantitative biology.

[116]  Hiroshi Kimura,et al.  Direct Imaging of DNA in Living Cells Reveals the Dynamics of Chromosome Formation , 1999, The Journal of cell biology.

[117]  Hesam Dehghani,et al.  Elucidating chromatin and nuclear domain architecture with electron spectroscopic imaging , 2008, Chromosome Research.

[118]  P. Bingham,et al.  Evidence for channeled diffusion of pre-mRNAs during nuclear RNA transport in metazoans , 1993, The Journal of cell biology.

[119]  N. Ringertz,et al.  Preparation and characterization of chick erythrocyte nuclei from heterokaryons. , 1974, Experimental cell research.

[120]  Thomas Cremer,et al.  Common themes and cell type specific variations of higher order chromatin arrangements in the mouse , 2005, BMC Cell Biology.

[121]  T. Williams,et al.  An archaeal origin of eukaryotes supports only two primary domains of life , 2013, Nature.

[122]  Ana Pombo,et al.  Replicon Clusters Are Stable Units of Chromosome Structure: Evidence That Nuclear Organization Contributes to the Efficient Activation and Propagation of S Phase in Human Cells , 1998, The Journal of cell biology.

[123]  Andrea M. Chiariello,et al.  Polymer models of chromatin organization , 2013, Front. Genet..

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

[125]  L. Peichl,et al.  LBR and Lamin A/C Sequentially Tether Peripheral Heterochromatin and Inversely Regulate Differentiation , 2013, Cell.

[126]  Benjamin J. Blencowe,et al.  The Nuclear Matrix: Past and Present , 1997 .

[127]  David Baddeley,et al.  High-precision structural analysis of subnuclear complexes in fixed and live cells via spatially modulated illumination (SMI) microscopy , 2008, Chromosome Research.

[128]  B. Steensel,et al.  Nuclear lamins are not required for lamina‐associated domain organization in mouse embryonic stem cells , 2015, EMBO reports.

[129]  Lothar Schermelleh,et al.  Fluorescence in situ hybridization applications for super-resolution 3D structured illumination microscopy. , 2013, Methods in molecular biology.

[130]  T. Pederson,et al.  Half a century of "the nuclear matrix". , 2000, Molecular biology of the cell.

[131]  E. Manders,et al.  Condensed chromatin domains in the mammalian nucleus are accessible to large macromolecules , 2003, EMBO reports.

[132]  C. J. Fecko,et al.  Revisiting point FRAP to quantitatively characterize anomalous diffusion in live cells. , 2013, The journal of physical chemistry. B.

[133]  Volker J Schmid,et al.  Remodeling of the Nuclear Envelope and Lamina during Bovine Preimplantation Development and Its Functional Implications , 2015, PloS one.

[134]  David R. Kelley,et al.  Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre , 2014, Nature Structural &Molecular Biology.

[135]  M. Tamura,et al.  Microenvironment and effect of energy depletion in the nucleus analyzed by mobility of multiple oligomeric EGFPs. , 2006, Biophysical journal.

[136]  Eugenio F Fornasiero,et al.  Super-resolution imaging for cell biologists: concepts, applications, current challenges and developments. , 2015, BioEssays : news and reviews in molecular, cellular and developmental biology.

[137]  B. van Steensel,et al.  Mechanisms and dynamics of nuclear lamina-genome interactions. , 2014, Current opinion in cell biology.

[138]  T. Cremer,et al.  Quantitative motion analysis of subchromosomal foci in living cells using four-dimensional microscopy. , 1999, Biophysical journal.

[139]  B. van Steensel,et al.  Genome-nuclear lamina interactions and gene regulation. , 2010, Current opinion in cell biology.

[140]  C. Cremer,et al.  Superresolution imaging of transcription units on newt lampbrush chromosomes , 2012, Chromosome Research.

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

[142]  T. Cremer,et al.  Correlative microscopy of individual cells: sequential application of microscopic systems with increasing resolution to study the nuclear landscape. , 2013, Methods in molecular biology.

[143]  D. Spector.  Higher order nuclear organization: three-dimensional distribution of small nuclear ribonucleoprotein particles. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[144]  Maxime Woringer,et al.  Geometry of the nucleus: a perspective on gene expression regulation. , 2014, Current opinion in chemical biology.

[145]  Thomas Cremer,et al.  Radial chromatin positioning is shaped by local gene density, not by gene expression , 2007, Chromosoma.

[146]  Thomas Cremer,et al.  Cell nucleus: Chromosome dynamics in nuclei of living cells , 1998, Current Biology.

[147]  Robert S Illingworth,et al.  Spatial genome organization: contrasting views from chromosome conformation capture and fluorescence in situ hybridization , 2014, Genes & development.

[148]  C. Woodcock,et al.  Nuclear matrix generation during reactivation of avian erythrocyte nuclei: an analysis of the protein traffic in cybrids. , 1986, Journal of cell science.

[149]  R. Berezney,et al.  Nuclear matrix: isolation and characterization of a framework structure from rat liver nuclei , 1977, The Journal of cell biology.

[150]  Karl Rohr,et al.  Chromatin domains and the interchromatin compartment form structurally defined and functionally interacting nuclear networks , 2006, Chromosome Research.

[151]  M. Gustafsson,et al.  Subdiffraction Multicolor Imaging of the Nuclear Periphery with 3D Structured Illumination Microscopy , 2008, Science.

[152]  U. Birk,et al.  Single molecule localization microscopy of the distribution of chromatin using Hoechst and DAPI fluorescent probes , 2014, Nucleus.

[153]  J. Lawrence,et al.  Stable C0T-1 Repeat RNA Is Abundant and Is Associated with Euchromatic Interphase Chromosomes , 2014, Cell.

[154]  Thomas Cremer,et al.  Chromosome order in HeLa cells changes during mitosis and early G1, but is stably maintained during subsequent interphase stages , 2003, The Journal of cell biology.

[155]  M. Beato,et al.  ADP-ribose derived Nuclear ATP is Required for Chromatin Remodeling and Hormonal Gene Regulation (97 charact) , 2014, bioRxiv.

[156]  Karsten Rippe,et al.  Retrieving the intracellular topology from multi-scale protein mobility mapping in living cells , 2014, Nature Communications.

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

[158]  C Cremer,et al.  Chromosome territories, interchromatin domain compartment, and nuclear matrix: an integrated view of the functional nuclear architecture. , 2000, Critical reviews in eukaryotic gene expression.

[159]  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.

[160]  Alberto Diaspro,et al.  High Data Output and Automated 3D Correlative Light–Electron Microscopy Method , 2008, Traffic.