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The pluripotent genome in three dimensions is shaped around pluripotency factors.

TitleThe pluripotent genome in three dimensions is shaped around pluripotency factors.
Publication TypeJournal Article
Year of Publication2013
Authorsde Wit E, Bouwman BAM, Zhu Y, Klous P, Splinter E, Verstegen MJAM, Krijger PHL, Festuccia N, Nora EP, Welling M, Heard E, Geijsen N, Poot RA, Chambers I, de Laat W
JournalNature
Volume501
Issue7466
Pagination227-31
Date Published2013 Sep 12
ISSN1476-4687
KeywordsAnimals, Binding Sites, Cell Line, Chromatin, Chromatin Immunoprecipitation, Chromosome Positioning, Embryonic Stem Cells, Enhancer Elements, Genetic, Genome, Homeodomain Proteins, Imaging, Three-Dimensional, Induced Pluripotent Stem Cells, Mice, Molecular Imaging, Octamer Transcription Factor-3, Organ Specificity, Pluripotent Stem Cells, Promoter Regions, Genetic, SOXB1 Transcription Factors
Abstract

It is becoming increasingly clear that the shape of the genome importantly influences transcription regulation. Pluripotent stem cells such as embryonic stem cells were recently shown to organize their chromosomes into topological domains that are largely invariant between cell types. Here we combine chromatin conformation capture technologies with chromatin factor binding data to demonstrate that inactive chromatin is unusually disorganized in pluripotent stem-cell nuclei. We show that gene promoters engage in contacts between topological domains in a largely tissue-independent manner, whereas enhancers have a more tissue-restricted interaction profile. Notably, genomic clusters of pluripotency factor binding sites find each other very efficiently, in a manner that is strictly pluripotent-stem-cell-specific, dependent on the presence of Oct4 and Nanog protein and inducible after artificial recruitment of Nanog to a selected chromosomal site. We conclude that pluripotent stem cells have a unique higher-order genome structure shaped by pluripotency factors. We speculate that this interactome enhances the robustness of the pluripotent state.

DOI10.1038/nature12420
Alternate JournalNature
PubMed ID23883933
Grant ListG0901533 / / Medical Research Council / United Kingdom