TY - JOUR
T1 - The transcription factor Zfp281 controls embryonic stem cell pluripotency by direct activation and repression of target genes
AU - Wang, Zheng Xu
AU - Teh, Christina Hui Leng
AU - Chan, Caroline Man Yee
AU - Chu, Ci
AU - Rossbach, Michael
AU - Kunarso, Galih
AU - Allapitchay, Tahira Bee
AU - Kee, Yew Wong
AU - Stanton, Lawrence W.
PY - 2008/11
Y1 - 2008/11
N2 - 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.
AB - 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.
KW - Differentiation
KW - Gene regulation
KW - Pluripotency
KW - Stem cells
KW - Transcription factor
UR - http://www.scopus.com/inward/record.url?scp=56249102803&partnerID=8YFLogxK
U2 - 10.1634/stemcells.2008-0443
DO - 10.1634/stemcells.2008-0443
M3 - Article
C2 - 18757296
AN - SCOPUS:56249102803
SN - 1066-5099
VL - 26
SP - 2791
EP - 2799
JO - Stem Cells
JF - Stem Cells
IS - 11
ER -