RT Journal Article
SR Electronic
T1 Transcription factors orchestrate dynamic interplay between genome topology and gene regulation during cell reprogramming
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 132456
DO 10.1101/132456
A1 Ralph Stadhouders
A1 Enrique Vidal
A1 François Serra
A1 Bruno Di Stefano
A1 François Le Dily
A1 Javier Quilez
A1 Antonio Gomez
A1 Samuel Collombet
A1 Clara Berenguer
A1 Yasmina Cuartero
A1 Jochen Hecht
A1 Guillaume Filion
A1 Miguel Beato
A1 Marc A. Marti-Renom
A1 Thomas Graf
YR 2017
UL http://biorxiv.org/content/early/2017/04/30/132456.abstract
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.