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KLF4 and PBX1 Directly Regulate NANOG Expression in Human Embryonic Stem Cells by Ken Kwok-Keung Chan; Jingyao Zhang; Na-Yu Chia; Yun-Shen Chan; Hui Shan Sim; Ker Sin Tan; Steve Kah-Weng Oh; Huck-Hui Ng; Andre Boon-Hwa Choo is a Medicine article available to read on EtoBox.

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## Abstract Insight into the regulation of core transcription factors is important for a better understanding of the molecular mechanisms that control self-renewal and pluripotency of human ESCs (hESCs). However, the transcriptional regulation of NANOG itself in hESCs has largely been elusive. We established a NANOG promoter luciferase reporter assay as a fast read-out for indicating the pluripotent status of hESCs. From the functional cDNA screens and NANOG promoter characterization, we successfully identified a zinc finger transcription factor KLF4 and a homeodomain transcription factor PBX1 as two novel transcriptional regulators that maintain the pluripotent and undifferentiated state of hESCs. We showed that both KLF4 and PBX1 mRNA and protein expression were downregulated during hESC differentiation. In addition, overexpression of KLF4 and PBX1 upregulated NANOG promoter activity and also the endogenous NANOG protein expression in hESCs. Direct binding of KLF4 on NANOG proximal promoter and PBX1 on a new upstream enhancer and proximal promoter were confirmed by chromatin immunoprecipitation and electrophoretic mobility shift assay. Knockdown of KLF4/PBX1 or mutation of KLF4/P

Who reads KLF4 and PBX1 Directly Regulate NANOG Expression in Human Embryonic Stem Cells?

Author

Ken Kwok-Keung Chan; Jingyao Zhang; Na-Yu Chia; Yun-Shen Chan; Hui Shan Sim; Ker Sin Tan; Steve Kah-Weng Oh; Huck-Hui Ng; Andre Boon-Hwa Choo

Publisher

Oxford University Press (OUP)

Published

2009

Language

EN

Field

Medicine (Health Sciences)