GSE129495
KLF4 binding is involved in the organization and regulation of 3D enhancer networks during acquisition and maintenance of pluripotency [RNA-seq]
Cell fate transitions are accompanied by global transcriptional, epigenetic and topological changes driven by transcription factors (TFs), as is strikingly exemplified in somatic cell reprogramming to pluripotent stem cells (PSCs) by OCT4, KLF4, SOX2 and cMYC. How TFs orchestrate the complex molecular changes around their targets in a temporal manner remains largely elusive. Here, using KLF4 as a paradigm, we provide the first TF-centric view of chromatin reorganization and the association to 3D enhancer rewiring and the transcriptional changes of linked genes during reprogramming of mouse embryonic fibroblasts to (MEFs) to PSCs. Inducible depletion of KLF factors in PSC caused a genome-wide decrease in connectivity of enhancers and disruption of KLF4 binding site from PSC-specific enhancers was sufficient to reduce expression of genes within the enhancer hub partly by impairing long-range contacts. Our study provides an integrative view of the intricate activities of a master regulator during a controlled cell fate transition and offers novel insights into the order and nature of molecular events that follow TF binding. Overall design: Integrative analysis of ChIP-seq, HiChIP, HiC, ATAC-seq, RNA-seq and 4C-seq techniques. RNA-seq TKO samples: RNA-seq was performed in 2 WT ESC cell populations and 2 ESC cell populations after KLF KO. RNA was extracted from 2 biological replicates at 0 hours (WT cells) and 24 hours after KLF KO.