title: The transcription factor Zfp281 controls embryonic stem cell pluripotency by direct activation and repression of target genes.
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. Disclosure of potential conflicts of interest is found at the end of this article.
authors.affiliation: Department of Hepatobilliary Surgery, Lanzhou Jin Cheng Hospital, Lan Zhou, People's Republic of China.
authors.forename: Zheng-Xu
authors.initials: ZX
authors.lastname: Wang
authors.forename: Christina Hui-Leng
authors.initials: CH
authors.lastname: Teh
authors.forename: Caroline Man-Yee
authors.initials: CM
authors.lastname: Chan
authors.forename: Ci
authors.initials: C
authors.lastname: Chu
authors.forename: Michael
authors.initials: M
authors.lastname: Rossbach
authors.forename: Galih
authors.initials: G
authors.lastname: Kunarso
authors.forename: Tahira Bee
authors.initials: TB
authors.lastname: Allapitchay
authors.forename: Kee Yew
authors.initials: KY
authors.lastname: Wong
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Stanton