Transcriptional Regulation of Nanog by OCT4 and SOX2*

By D. Rodda, Joon-Lin Chew, L. Lim, Yuin Han Loh, Bei Wang, Huck-Hui Ng, Paul Robson. Journal of Biological Chemistry, 2005

1,178 citations recorded by the source corpus.

Nanog, Sox2, and Oct4 are transcription factors all essential to maintaining the pluripotent embryonic stem cell phenotype. Through a cooperative interaction, Sox2 and Oct4 have previously been described to drive pluripotent-specific expression of a number of genes. We now extend the list of Sox2-Oct4 target genes to include Nanog. Within the Nanog proximal promoter, we identify a composite sox-oct cis-regulatory element essential for Nanog pluripotent transcription. This element is conserved over 250 million years of cumulative evolution within the eutherian mammals. A Nanog proximal promoter-EGFP (enhanced green fluorescent protein) reporter transgene recapitulates endogenous Nanog mRNA expression in embryonic stem cells and their differentiated derivatives. Sox2 and Oct4 interaction with the Nanog promoter was confirmed through mutagenesis and in vitro binding assays. Electrophoretic mobility shift assays indicate that the Sox2-Oct4 heterodimer forms more efficiently on the composite element within Nanog than the similar element within Fgf4. Using chromatin immunoprecipitation, we show that Oct4 and Sox2 bind to the Nanog promoter in living mouse and human embryonic stem cells. Furthermore, by specific knockdown of Oct4 and Sox2 mRNA by RNA interference in embryonic stem cells, we provide genetic evidence for a link between Oct4, Sox2, and the Nanog promoter. These studies extend the understanding of the pluripotent genetic regulatory network within which the Sox2-Oct4 complex are at the top of the regulatory hierarchy.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3bf9f5319e4d9b5a9085fe9a97ab80c738968722

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In Molecular Biology

1. Richard A. Young
2. R. Jaenisch
3. Tong Ihn Lee
4. A. Soufi
5. H. Niwa
6. K. Zaret
7. S. Levine
8. M. Guenther

Citations in the corpus

• How is pluripotency determined and maintained? (2007, background): “However, although it has been reported that Nanog expression is partly regulated by Oct3/4 and Sox2, a member of the Sox (SRY-related HMG box) family (Kuroda et al., 2005; Rodda et al., 2005), and although artificial Nanog expression can block the differentiation of ES cells into primitive endoderm ”
• MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. (2009, positive): “Consistent with a previous report (Rodda et al., 2005), the positive control NANOG promoter element ( 0.”
• Core transcriptional regulatory circuitry in human embryonic stem cells. (2005, background): “…SOX2, NANOG, LEFTY2/ EBAF, CDX2, HAND1, DPPA4, GJA1/CONNEXIN43, FOXO1A, CRIPTO/TDGF1, and ZIC3 (Abeyta et al., 2004; Brandenberger et al., 2004; Catena et al., 2004; Kuroda et al., 2005; Niwa, 2001; Okumura-Nakanishi et al., 2005; Rodda et al., 2005; Sato et al., 2003; Wei et al., 2005) (Table S2).”
• Pioneer Transcription Factors Target Partial DNA Motifs on Nucleosomes to Initiate Reprogramming (2015, positive): “) expressed, recombinant O, S, K, and M proteins bound to DNA probes containing canonical motifs, as previously reported for the purified DBDs (Farina et al., 2004; Nakatake et al., 2006; Rodda et al., 2005) (Figure S1B; Table 1), and bound with much lower affinity to non-specific DNA sequences of t”
• Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst. (2010, background): “In addition to the downregulation of Fgfr2 , cells expressing Sox2 earlier would be in a position to replenish depleting levels of maternal Sox2, thus maintaining the expression of key pluripotency Sox2 target genes such as Nanog (Rodda et al., 2005; Silva et al., 2009).”