Klf4 organizes long-range chromosomal interactions with the OCT4 locus inreprogramming andpluripotency

Zong Wei, Fan Gao, Sewoon Kim, Hongzhen Yang, Jungmook Lyu, Woojin An, Kai Wang, Wange Lu

Research output: Contribution to journalArticlepeer-review

136 Scopus citations

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 longrange 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 higherorder chromatin structure in maintaining and inducing pluripotency. 2013

Original languageEnglish (US)
Pages (from-to)36-47
Number of pages12
JournalCell Stem Cell
Volume13
Issue number1
DOIs
StatePublished - Jul 3 2013

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'Klf4 organizes long-range chromosomal interactions with the OCT4 locus inreprogramming andpluripotency'. Together they form a unique fingerprint.

Cite this