Open AccessThe Transcription Factor Zfp281 Controls Embryonic Stem Cell Pluripotency by Direct Activation and Repression of Target Genes
Author(s) -
Wang ZhengXu,
Teh Christina HuiLeng,
Chan Caroline ManYee,
Chu Ci,
Rossbach Michael,
Kunarso Galih,
Allapitchay Tahira Bee,
Wong Kee Yew,
Stanton Lawrence W.
Publication year - 2008
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2008-0443
Subject(s) - homeobox protein nanog , biology , sox2 , rex1 , transcription factor , chromatin immunoprecipitation , nanog homeobox protein , zinc finger transcription factor , embryonic stem cell , promoter , gene knockdown , regulation of gene expression , microbiology and biotechnology , genetics , gene , zinc finger , gene expression , induced pluripotent stem cell
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. Disclosure of potential conflicts of interest is found at the end of this article.