E-GEOD-37275 - The pluripotent genome in three dimensions is shaped around pluripotency factors
Released on 24 July 2013, last updated on 3 May 2014
It is becoming increasingly clear that the shape of the genome importantly influences transcription regulation. Pluripotent stem cells (PSCs) such as embryonic stem cells (ESCs) were recently shown to organize their chromosomes into topological domains that are largely invariant between cell types. Here, we applied 4C technology and combined ChIP-seq with Hi-C data to demonstrate that inactive chromatin is unusually disorganized in PSC nuclei. We show that gene promoters engage in contacts between topological domains in a largely tissue-independent manner while enhancers have a more tissue-restricted interaction profile. Most strikingly, genomic clusters of pluripotency factor binding sites find each other very efficiently, in a manner that is strictly PSC-specific, dependent on the presence of Oct4 and Nanog protein and inducible upon 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. 4C-seq was performed on a range of viewpoints in pluripotent (2x ESC, iPSC) and differentiated (neural precursor cells and astrocytes) cell lines.
Elzo de Wit <email@example.com>, Britta Bouwman, Edith Heard, Elphege Nora, Erik Splinter, Ian Chambers, Maaike Welling, Marjon Verstegen, Nicola Festuccia, Niels Geijsen, Peter Krijger, Petra Klous, Raymond Poot, Wouter de Laat, Yun Zhu