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Three-dimensional genome architecture: players and mechanisms
Ana Pombo1 and Niall Dillon2
Abstract | The different cell types of an organism share the same DNA, but during cell differentiation their genomes undergo diverse structural and organizational changes that affect gene expression and other cellular functions. These can range from large-scale folding of whole chromosomes or of smaller genomic regions, to the re-organization of local interactions between enhancers and promoters, mediated by the binding of transcription factors and chromatin looping. The higher-order organization of chromatin is also influenced by the specificity of the contacts that it makes with nuclear structures such as the lamina. Sophisticated methods for mapping chromatin contacts are generating genome-wide data that provide deep insights into the formation of chromatin interactions, and into their roles in the organization and function of the eukaryotic cell nucleus.
Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max Delbrck Center for Molecular Medicine, RobertRoessle Strasse, 13125 Berlin-Buch, Germany.
Gene Regulation and Chromatin Group, MRCClinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK. e-mails: mailto:ana.pombo%40mdc-berlin.de?subject=
Web End [email protected] ; mailto:[email protected]
Web End [email protected] doi:10.1038/nrm3965 Published online 11 March 2015
The 2-metre length of DNA in a mammalian cell is organized into chromosomes, which are packaged and folded through various mechanisms and occupy discrete positions in the nucleus. The multiple levels of DNA folding generate extensive contacts between different genomic regions. These contacts are influenced by the proximity of DNA sequences to one another, by the folding architecture of local and long-range chromatin contacts and by proteins that associate directly or indirectly with the DNA. Packing of chromosomes in the nucleus also brings them into contact with one another and with nuclear compartments, such as the nucleolus and the nuclear envelope. As cells progress through the cell cycle and as they differentiate into specialized cell types, their chromosomes undergo structural re-organizations that influence gene expression and cell behaviour and function, which in turn modulate the organization of contacts between chromosomal regions. Techniques such as
chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) have yielded large amounts of data on transcription factor binding and post-translational his-tone modifications in a range of cell types. Increasingly sophisticated methods of chromatin conformation capture...