TY - JOUR
T1 - Elevating the levels of Sox2 in embryonal carcinoma cells and embryonic stem cells inhibits the expression of Sox2:Oct-3/4 target genes
AU - Boer, Brian
AU - Kopp, Janel
AU - Mallanna, Sunil
AU - Desler, Michelle
AU - Chakravarthy, Harini
AU - Wilder, Phillip J.
AU - Bernadt, Cory
AU - Rizzino, Angie
N1 - Funding Information:
*To whom correspondence should be addressed. Tel: þ4025596338; Fax: þ4025593339; E-mail: [email protected] yThis work was supported by a grant from the National Institute of General Medical Sciences (GM80751). Core facilities used in connection with this work was supported in part by a Cancer Center Support Grant (CA36727). Brian Boer and Janel Kopp were supported in part by Cancer Biology Training Grant (CA09476).
Funding Information:
Charles Kuszynski and Linda Wilkie of the Cell Analysis Core Facility are thanked for their technical advice and assistance. This work was supported by a grant from the National Institute of General Medical Sciences (GM80751). Core facilities used in connection with this work was supported in part by a Cancer Center Support Grant (CA36727). B.B. and J.K. were supported in part by a Cancer Biology Training Grant (CA09476). Funding to pay the Open Access publication charge was provided by the grant information: GM80751.
PY - 2007/3
Y1 - 2007/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34247887724&partnerID=8YFLogxK
U2 - 10.1093/nar/gkm059
DO - 10.1093/nar/gkm059
M3 - Article
C2 - 17324942
AN - SCOPUS:34247887724
SN - 0305-1048
VL - 35
SP - 1773
EP - 1786
JO - Nucleic acids research
JF - Nucleic acids research
IS - 6
ER -