The pluripotent genome in three dimensions is shaped around pluripotency factors

TY - JOUR

T1 - The pluripotent genome in three dimensions is shaped around pluripotency factors

AU - de Wit, E.

AU - Bouwman, B.A.M.

AU - Zhu, Y.

AU - Klous, P.

AU - Splinter, E.

AU - Verstegen, M.J.

AU - Krijger, P.H.

AU - Festuccia, N.

AU - Nora, E.P.

AU - Welling, M.

AU - Heard, E.

AU - Geijsen, N.

AU - Poot, R.A.

AU - Chambers, I.

AU - de Laat, W.

N1 - Reporting year: 2013

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

U2 - 10.1038/nature12420

DO - 10.1038/nature12420

M3 - Article

SN - 0028-0836

VL - 501

SP - 227

EP - 231

JO - Nature

JF - Nature

IS - 7466

ER -