Klf4 Organizes Long-Range Chromosomal Interactions with the Oct4 Locus in Reprogramming and Pluripotency.

Journal: 
Cell Stem Cell
Publication Year: 
2013
Authors: 
Zong Wei , Fan Gao , Sewoon Kim , Hongzhen Yang , Jungmook Lyu , Woojin An , Kai Wang , Wange Lu
Public Summary: 
Scientific Abstract: 
Epigenetic mechanisms underlying somatic reprogramming have been extensively studied, but little is known about the nuclear architecture of pluripotent stem cells (PSCs). Using circular chromosome conformation capture with high-throughput sequencing (4C-seq) and fluorescence in situ hybridization (FISH), we identified chromosomal regions that colocalize frequently with the Oct4 locus in PSCs. These PSC-specific long-range interactions are established prior to transcriptional activation of endogenous Oct4 during reprogramming to induced PSCs and are facilitated by Klf4-mediated recruitment of cohesin. Depletion of Klf4 leads to unloading of cohesin at the Oct4 enhancer and disrupts long-range interactions prior to loss of Oct4 transcription and subsequent PSC differentiation, suggesting a causative role for Klf4 in facilitating long-range interactions independent of its transcriptional activity. Taken together, our results delineate the basic nuclear organization at the Oct4 locus in PSCs and suggest a functional role for Klf4-mediated higher-order chromatin structure in maintaining and inducing pluripotency.

© 2013 California Institute for Regenerative Medicine