The transcription factor Zfp281 controls embryonic stem cell pluripotency by direct activation and repression of target genes

Zheng Xu Wang, Christina Hui Leng Teh, Caroline Man Yee Chan, Ci Chu, Michael Rossbach, Galih Kunarso, Tahira Bee Allapitchay, Yew Wong Kee, Lawrence W. Stanton

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)

Abstract

Oct4, Sox2, and Nanog are key components of a core transcriptional regulatory network that controls the ability of embryonic stem cells to differentiate into all cell types. Here we show that Zfp281, a zinc finger transcription factor, is a key component of the network and that it is required to maintain pluripotency. Zfp281 was shown to directly activate Nanog expression by binding to a site in the promoter in very close proximity to the Oct4 and Sox2 binding sites. We present data showing that Zfp281 physically interacts with Oct4, Sox2, and Nanog. Chromatin immunoprecipitation experiments identified 2,417 genes that are direct targets for regulation by Zfp281, including several transcription factors that are known regulators of pluripotency, such as Oct4, Sox2, and Nanog. Gene expression microarray analysis indicated that some Zfp281 target genes were activated, whereas others were repressed, upon knockdown of Zfp281. The identification of both activation and repression domains within Zfp281 suggests that this transcription factor plays bifunctional roles in regulating gene expression within the network.

Original languageEnglish
Pages (from-to)2791-2799
Number of pages9
JournalStem Cells
Volume26
Issue number11
DOIs
Publication statusPublished - Nov 2008
Externally publishedYes

Keywords

  • Differentiation
  • Gene regulation
  • Pluripotency
  • Stem cells
  • Transcription factor

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