Despite its exciting potential, chemical induction of pluripotency (CIP) efficiency remains low and the mechanisms are poorly understood. We report the development of an efficient two-step serum- and replating-free CIP protocol and the associated chromatin accessibility dynamics (CAD) by assay for transposase-accessible chromatin (ATAC)-seq. CIP reorganizes the somatic genome to an intermediate state that is resolved under 2iL condition by re-closing previously opened loci prior to pluripotency acquisition with gradual opening of loci enriched with motifs for the OCT/SOX/KLF families. Bromodeoxyuridine, a critical ingredient of CIP, is responsible for both closing and opening critical loci, at least in part by preventing the opening of loci enriched with motifs for the AP1 family and facilitating the opening of loci enriched with SOX/KLF/GATA motifs. These changes differ markedly from CAD observed during Yamanaka-factor-driven reprogramming. Our study provides insights into small-molecule-based reprogramming mechanisms and reorganization of nuclear architecture associated with cell-fate decisions.
Pubmed ID: 29625068 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets BrdU antibody produced in mouse
View all literature mentionsThis polyclonal targets Histone H3 (tri methyl K4)
View all literature mentionsThis polyclonal targets H3K9me3
View all literature mentionsThis polyclonal targets H3K27ac
View all literature mentionsThis monoclonal targets Human/Mouse Stage-specific Embryonic Ag-1 MAb (Cl MC-480)
View all literature mentionsThis polyclonal targets SOX2
View all literature mentionsThis monoclonal targets Oct-3/4
View all literature mentions