Evidence that transcription factor AP-2γ is not required for Oct4 repression in mouse blastocysts.

In mouse blastocysts segregation of the inner cell mass (ICM) and the trophectoderm (TE) is regulated by the mutually antagonistic effects of the transcription factors Oct4 and Cdx2 expressed in the ICM and TE, respectively. In contrast, in other species such as bovine and human, Oct4 is not restric...

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Autores principales: Inchul Choi, Timothy S Carey, Catherine A Wilson, Jason G Knott
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:50084a6426c54733a7afe91e10ae62242021-11-18T07:43:22ZEvidence that transcription factor AP-2γ is not required for Oct4 repression in mouse blastocysts.1932-620310.1371/journal.pone.0065771https://doaj.org/article/50084a6426c54733a7afe91e10ae62242013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23741512/?tool=EBIhttps://doaj.org/toc/1932-6203In mouse blastocysts segregation of the inner cell mass (ICM) and the trophectoderm (TE) is regulated by the mutually antagonistic effects of the transcription factors Oct4 and Cdx2 expressed in the ICM and TE, respectively. In contrast, in other species such as bovine and human, Oct4 is not restricted to the ICM and continues to be expressed in the Cdx2-positive TE. A recent comparative study of the bovine and mouse Oct4 promoters revealed that additional mechanisms might act in conjunction with Cdx2 to downregulate Oct4 expression in the mouse TE lineage. For instance, the mouse Oct4 distal enhancer contains an AP-2γ (Tcfap2c) binding motif that is absent in the bovine and human Oct4 distal enhancer. Nonetheless, the functional relevance of Tcfap2c in Oct4 repression during mouse preimplantation development was not tested. To elucidate the role of Tcfap2c in Oct4 expression an RNA interference approach was utilized. Depletion of Tcfap2c triggered a decrease in Oct4 expression at the 8-cell and morula stage. Remarkably, at the blastocyst stage depletion of Tcfap2c and/or its family member Tcfap2a had no effect on Oct4 repression. To test whether Tcfap2c interacts with Oct4 to positively regulate Oct4 expression, chromatin immunoprecipitation and in situ co-immunoprecipitation analyses were performed. These experiments revealed Tcfap2c and Oct4 binding were enriched at the Oct4 distal enhancer in embryonic stem (ES) cells, but were rapidly lost during differentiation into trophoblast-like cells when Oct4 became repressed. Moreover, Tcfap2c and Oct4 interactions were detected at the morula stage, but were lost during blastocyst formation. In summary, these data demonstrate that Tcfap2c is not required for Oct4 silencing in mouse blastocysts, but may be necessary for the maintenance of Oct4 expression during the 8 cell-to-morula transition. These findings support the notion Cdx2 is the predominant negative regulator of Oct4 expression during blastocyst formation in mice.Inchul ChoiTimothy S CareyCatherine A WilsonJason G KnottPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e65771 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Inchul Choi
Timothy S Carey
Catherine A Wilson
Jason G Knott
Evidence that transcription factor AP-2γ is not required for Oct4 repression in mouse blastocysts.
description In mouse blastocysts segregation of the inner cell mass (ICM) and the trophectoderm (TE) is regulated by the mutually antagonistic effects of the transcription factors Oct4 and Cdx2 expressed in the ICM and TE, respectively. In contrast, in other species such as bovine and human, Oct4 is not restricted to the ICM and continues to be expressed in the Cdx2-positive TE. A recent comparative study of the bovine and mouse Oct4 promoters revealed that additional mechanisms might act in conjunction with Cdx2 to downregulate Oct4 expression in the mouse TE lineage. For instance, the mouse Oct4 distal enhancer contains an AP-2γ (Tcfap2c) binding motif that is absent in the bovine and human Oct4 distal enhancer. Nonetheless, the functional relevance of Tcfap2c in Oct4 repression during mouse preimplantation development was not tested. To elucidate the role of Tcfap2c in Oct4 expression an RNA interference approach was utilized. Depletion of Tcfap2c triggered a decrease in Oct4 expression at the 8-cell and morula stage. Remarkably, at the blastocyst stage depletion of Tcfap2c and/or its family member Tcfap2a had no effect on Oct4 repression. To test whether Tcfap2c interacts with Oct4 to positively regulate Oct4 expression, chromatin immunoprecipitation and in situ co-immunoprecipitation analyses were performed. These experiments revealed Tcfap2c and Oct4 binding were enriched at the Oct4 distal enhancer in embryonic stem (ES) cells, but were rapidly lost during differentiation into trophoblast-like cells when Oct4 became repressed. Moreover, Tcfap2c and Oct4 interactions were detected at the morula stage, but were lost during blastocyst formation. In summary, these data demonstrate that Tcfap2c is not required for Oct4 silencing in mouse blastocysts, but may be necessary for the maintenance of Oct4 expression during the 8 cell-to-morula transition. These findings support the notion Cdx2 is the predominant negative regulator of Oct4 expression during blastocyst formation in mice.
format article
author Inchul Choi
Timothy S Carey
Catherine A Wilson
Jason G Knott
author_facet Inchul Choi
Timothy S Carey
Catherine A Wilson
Jason G Knott
author_sort Inchul Choi
title Evidence that transcription factor AP-2γ is not required for Oct4 repression in mouse blastocysts.
title_short Evidence that transcription factor AP-2γ is not required for Oct4 repression in mouse blastocysts.
title_full Evidence that transcription factor AP-2γ is not required for Oct4 repression in mouse blastocysts.
title_fullStr Evidence that transcription factor AP-2γ is not required for Oct4 repression in mouse blastocysts.
title_full_unstemmed Evidence that transcription factor AP-2γ is not required for Oct4 repression in mouse blastocysts.
title_sort evidence that transcription factor ap-2γ is not required for oct4 repression in mouse blastocysts.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/50084a6426c54733a7afe91e10ae6224
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AT timothyscarey evidencethattranscriptionfactorap2gisnotrequiredforoct4repressioninmouseblastocysts
AT catherineawilson evidencethattranscriptionfactorap2gisnotrequiredforoct4repressioninmouseblastocysts
AT jasongknott evidencethattranscriptionfactorap2gisnotrequiredforoct4repressioninmouseblastocysts
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