PT  - JOURNAL ARTICLE
AU  - Ralph Stadhouders
AU  - Enrique Vidal
AU  - François Serra
AU  - Bruno Di Stefano
AU  - François Le Dily
AU  - Javier Quilez
AU  - Antonio Gomez
AU  - Samuel Collombet
AU  - Clara Berenguer
AU  - Yasmina Cuartero
AU  - Jochen Hecht
AU  - Guillaume Filion
AU  - Miguel Beato
AU  - Marc A. Marti-Renom
AU  - Thomas Graf
TI  - Transcription factors orchestrate dynamic interplay between genome topology and gene regulation during cell reprogramming
AID  - 10.1101/132456
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 132456
4099  - http://biorxiv.org/content/early/2017/04/30/132456.short
4100  - http://biorxiv.org/content/early/2017/04/30/132456.full
AB  - Chromosomal architecture is known to influence gene expression, yet its role in controlling cell fate remains poorly understood. Reprogramming of somatic cells into pluripotent stem cells by the transcription factors (TFs) Oct4, Sox2, Klf4 and Myc offers an opportunity to address this question but is severely limited by the low proportion of responding cells. We recently developed a highly efficient reprogramming protocol that synchronously converts somatic into pluripotent stem cells. Here, we employ this system to integrate time-resolved changes in genome topology with gene expression, TF binding and chromatin state dynamics. This revealed that TFs drive topological genome reorganization at multiple architectural levels, which often precedes changes in gene expression. Removal of locus-specific topological barriers can explain why pluripotency genes are activated sequentially, instead of simultaneously, during reprogramming. Taken together, our study implicates genome topology as an instructive force for implementing transcriptional programs and cell fate in mammals.