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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Serial genomic inversions induce tissue-specific architectural stripes, gene misexpression and congenital malformations.
Katerina Kraft,Katerina Kraft,Katerina Kraft,Andreas Magg,Verena Heinrich,Christina Riemenschneider,Robert Schöpflin,Robert Schöpflin,Julia Markowski,Daniel M. Ibrahim,Daniel M. Ibrahim,Rocio Acuna-Hidalgo,Rocio Acuna-Hidalgo,Alexandra Despang,Alexandra Despang,Guillaume Andrey,Guillaume Andrey,Lars Wittler,Bernd Timmermann,Martin Vingron,Stefan Mundlos,Stefan Mundlos +21 more
TL;DR: It is shown that chromosomal inversions that relocate a limb enhancer can establish asymmetric stripes of the enhancer with downstream genes, resulting in ectopic gene expression and limb phenotypes, and architectural stripes are a frequent feature of developmental three-dimensional genome architecture often associated with active enhancers.
Journal ArticleDOI
Genome-wide studies of CCCTC-binding factor (CTCF) and cohesin provide insight into chromatin structure and regulation.
Bum Kyu Lee,Vishwanath R. Iyer +1 more
TL;DR: This partnership between CTCF and cohesin is emerging as a novel and perhaps pivotal aspect of gene regulatory mechanisms, in addition to playing a role in the organization of higher order chromatin architecture.
Journal ArticleDOI
Binding of the Rett syndrome protein, MeCP2, to methylated and unmethylated DNA and chromatin.
TL;DR: Mechanistic studies indicate that the binding of MeCP2 to chromatin results in compaction into local (secondary) and global (tertiary) higher order structures, and the potential ramifications of this work for in vivo function are discussed.
Journal ArticleDOI
Integration of Hi-C and ChIP-seq data reveals distinct types of chromatin linkages.
Xun Lan,Heather Witt,Koichi R. Katsumura,Zhenqing Ye,Qianben Wang,Emery H. Bresnick,Peggy J. Farnham,Victor X. Jin +7 more
TL;DR: This work, in combination with previous studies linking regulation by GATA factors with c-Jun and BRG1, provides genome-wide evidence that Hi-C data identify sets of biologically relevant interacting loci.
Journal ArticleDOI
Chromatin regulation at the frontier of synthetic biology
TL;DR: These studies lay the foundation for biomedical and biotechnological engineering applications that could take advantage of the unique combinatorial and spatiotemporal layers of chromatin regulation to create synthetic systems of unprecedented sophistication.
References
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