Elevating the levels of Sox2 in embryonal carcinoma cells and embryonic stem cells inhibits the expression of Sox2:Oct-3/4 target genes

Brian Boer, Janel Kopp, Sunil Mallanna, Michelle Desler, Harini Chakravarthy, Phillip J. Wilder, Cory Bernadt, A Angie Rizzino

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Recent studies have identified large sets of genes in embryonic stem and embryonal carcinoma cells that are associated with the transcription factors Sox2 and Oct-3/4. Other studies have shown that Sox2 and Oct-3/4 work together cooperatively to stimulate the transcription of their own genes as well as a network of genes required for embryogenesis. Moreover, small changes in the levels of Sox2:Oct-3/4 target genes alter the fate of stem cells. Although positive feedforward and feedback loops have been proposed to explain the activation of these genes, little is known about the mechanisms that prevent their overexpression. Here, we demonstrate that elevating Sox2 levels inhibits the endogenous expression of five Sox2:Oct-3/4 target genes. In addition, we show that Sox2 repression is dependent on the binding sites for Sox2 and Oct-3/4. We also demonstrate that inhibition is dependent on the C-terminus of Sox2, which contains its transactivation domain. Finally, our studies argue that overexpression of neither Oct-3/4 nor Nanog broadly inhibits Sox2:Oct-3/4 target genes. Collectively, these studies provide new insights into the diversity of mechanisms that control Sox2:Oct-3/4 target genes and argue that Sox2 functions as a molecular rheostat for the control of a key transcriptional regulatory network.

Original languageEnglish (US)
Pages (from-to)1773-1786
Number of pages14
JournalNucleic Acids Research
Volume35
Issue number6
DOIs
StatePublished - Mar 1 2007

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Embryonal Carcinoma Stem Cells
Embryonic Stem Cells
Genes
Gene Regulatory Networks
Transcriptional Activation
Octamer Transcription Factor-3
Embryonic Development
Stem Cells
Binding Sites

ASJC Scopus subject areas

  • Genetics

Cite this

Elevating the levels of Sox2 in embryonal carcinoma cells and embryonic stem cells inhibits the expression of Sox2:Oct-3/4 target genes. / Boer, Brian; Kopp, Janel; Mallanna, Sunil; Desler, Michelle; Chakravarthy, Harini; Wilder, Phillip J.; Bernadt, Cory; Rizzino, A Angie.

In: Nucleic Acids Research, Vol. 35, No. 6, 01.03.2007, p. 1773-1786.

Research output: Contribution to journalArticle

Boer, Brian ; Kopp, Janel ; Mallanna, Sunil ; Desler, Michelle ; Chakravarthy, Harini ; Wilder, Phillip J. ; Bernadt, Cory ; Rizzino, A Angie. / Elevating the levels of Sox2 in embryonal carcinoma cells and embryonic stem cells inhibits the expression of Sox2:Oct-3/4 target genes. In: Nucleic Acids Research. 2007 ; Vol. 35, No. 6. pp. 1773-1786.
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