Comprehensive mapping of long-range interactions reveals folding principles of the human genome.
Erez Lieberman Aiden,Nynke L. van Berkum,Louise Williams,Maxim Imakaev,Tobias Ragoczy,Tobias Ragoczy,Agnes Telling,Agnes Telling,Ido Amit,Bryan R. Lajoie,Peter J. Sabo,Michael O. Dorschner,Richard Sandstrom,Bradley E. Bernstein,Bradley E. Bernstein,Michaël Bender,Mark Groudine,Mark Groudine,Andreas Gnirke,John A. Stamatoyannopoulos,Leonid A. Mirny,Eric S. Lander,Eric S. Lander,Job Dekker +23 more
TLDR
Hi-C is described, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing and demonstrates the power of Hi-C to map the dynamic conformations of entire genomes.Abstract:
We describe Hi-C, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. We constructed spatial proximity maps of the human genome with Hi-C at a resolution of 1 megabase. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.read more
Citations
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Evolutionary comparison reveals that diverging CTCF sites are signatures of ancestral topological associating domains borders.
Carlos Gómez-Marín,Juan J. Tena,Rafael D. Acemel,Macarena López-Mayorga,Silvia Naranjo,Elisa de la Calle-Mustienes,Ignacio Maeso,Leonardo Beccari,Ivy Aneas,Erika Vielmas,Paola Bovolenta,Marcelo A. Nobrega,Jaime J. Carvajal,José Luis Gómez-Skarmeta +13 more
TL;DR: By disrupting the conserved TAD border in one of the zebrafish Six clusters, it is demonstrated that this border is critical for preventing competition between promoters and enhancers located in separated RLs, thereby generating different expression patterns in genes located in close genomic proximity.
Journal ArticleDOI
Cohesin regulates tissue-specific expression by stabilizing highly occupied cis-regulatory modules
Andre J. Faure,Dominic Schmidt,Stephen Watt,Petra C. Schwalie,Michael D. Wilson,Huiling Xu,Huiling Xu,Robert G. Ramsay,Robert G. Ramsay,Duncan T. Odom,Paul Flicek,Paul Flicek +11 more
TL;DR: Evidence from statistical analyses in wild-type cells, and comparisons to maps of TF binding in Rad21-cohesin haploinsufficient mouse liver, suggests that cohesin helps to stabilize large protein-DNA complexes.
Journal ArticleDOI
Neuron-specific signatures in the chromosomal connectome associated with schizophrenia risk.
Prashanth Rajarajan,Tyler M. Borrman,Will Liao,Nadine Schrode,Erin Flaherty,Charlize Casiño,Samuel K. Powell,Chittampalli Yashaswini,Elizabeth A. LaMarca,Bibi Kassim,Behnam Javidfar,Sergio Espeso-Gil,Aiqun Li,Hyejung Won,Daniel H. Geschwind,Seok-Man Ho,Matthew L. MacDonald,Gabriel E. Hoffman,Panos Roussos,Bin Zhang,Chang-Gyu Hahn,Zhiping Weng,Kristen J. Brennand,Schahram Akbarian +23 more
TL;DR: This study shows that neural differentiation is associated with highly cell type–specific 3DG remodeling, which is paralleled by an expansion of3DG space associated with SZ risk, and tests whether the neural cell–specific SZ-related “chromosomal connectome” showed evidence of coordinated transcriptional regulation and proteomic interaction of the participating genes.
Journal ArticleDOI
Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci
Daniel Smeets,Daniel Smeets,Yolanda Markaki,Volker Schmid,Felix Kraus,Felix Kraus,Anna Tattermusch,Andrea Cerase,Michael Sterr,Susanne Fiedler,Justin Demmerle,Jens Popken,Heinrich Leonhardt,Neil Brockdorff,Thomas Cremer,Lothar Schermelleh,Lothar Schermelleh,Marion Cremer +17 more
TL;DR: 3D-SIM provides experimental evidence for profound differences between the functional architecture of transcriptionally active CTs and the Barr body, and proposes that the PR and macromolecular complexes in IC channels together form the transcriptionally permissive active nuclear compartment (ANC).
Journal ArticleDOI
On TADs and LADs: Spatial Control Over Gene Expression
TL;DR: The results shed light on the relevance of topologically associated domains and Lamina-associated domains for transcriptional regulation, and address specifically how chromatin sequestration influences cell fate decisions during organismal development.
References
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