Local Genome Topology Can Exhibit an Incompletely Rewired 3D-Folding State During Somatic Cell Reprogramming

The pluripotent genome is folded in a hierarchy of sophisticated topologies that markedly reconfigure during cell fate transitions. A critical unknown is whether chromatin folding is reversible and functionally linked to the re-establishment of pluripotency in somatic cell reprogramming. Here we integrate classic epigenetic marks with high-resolution architecture maps in embryonic stem (ES) cells, ES-derived neural progenitor cells (NPCs) and NPC-derived induced pluripotent stem (iPS) cells. Collectively we demonstrate that chromatin architecture is only partially reconfigured during somatic cell reprogramming and that pluripotent elements can retain architectural memory from their somatic cell of origin. Overall design: Analysis of higher-order chromatin chromatin architecture and gene expression in mouse ES cells, primary NPCs and NPC-derived iPSCs.