@article {Stadhouders132456, author = {Ralph Stadhouders and Enrique Vidal and Fran{\c c}ois Serra and Bruno Di Stefano and Fran{\c c}ois Le Dily and Javier Quilez and Antonio Gomez and Samuel Collombet and Clara Berenguer and Yasmina Cuartero and Jochen Hecht and Guillaume Filion and Miguel Beato and Marc A. Marti-Renom and Thomas Graf}, title = {Transcription factors orchestrate dynamic interplay between genome topology and gene regulation during cell reprogramming}, elocation-id = {132456}, year = {2017}, doi = {10.1101/132456}, publisher = {Cold Spring Harbor Laboratory}, abstract = {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.}, URL = {https://www.biorxiv.org/content/early/2017/04/30/132456}, eprint = {https://www.biorxiv.org/content/early/2017/04/30/132456.full.pdf}, journal = {bioRxiv} }