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Role of Oct4 in the early embryo development.

Wu G, Schöler HR - Cell Regen (Lond) (2014)

Bottom Line: Oct4 of maternal origin is postulated to play critical role in defining totipotency and inducing pluripotency during embryonic development.These results indicate that Oct4 is not essential for the initiation of pluripotency, in contrast to its critical role in maintaining pluripotency.This conclusion is further supported by the formation of Oct4-GFP- and Nanog- expressing inner cell masses (ICMs) in embryos with complete inactivation of both maternal and zygotic Oct4 expression and the reprogramming of fibroblasts into fully pluripotent cells by Oct4-deficient oocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany.

ABSTRACT
Oct4 is a key component of the pluripotency regulatory network, and its reciprocal interaction with Cdx2 has been shown to be a determinant of either the self-renewal of embryonic stem cells (ESCs) or their differentiation into trophoblast. Oct4 of maternal origin is postulated to play critical role in defining totipotency and inducing pluripotency during embryonic development. However, the genetic elimination of maternal Oct4 using a Cre-lox approach in mouse revealed that the establishment of totipotency in maternal Oct4-depleted embryos was not affected, and that these embryos could complete full-term development without any obvious defect. These results indicate that Oct4 is not essential for the initiation of pluripotency, in contrast to its critical role in maintaining pluripotency. This conclusion is further supported by the formation of Oct4-GFP- and Nanog- expressing inner cell masses (ICMs) in embryos with complete inactivation of both maternal and zygotic Oct4 expression and the reprogramming of fibroblasts into fully pluripotent cells by Oct4-deficient oocytes.

No MeSH data available.


Related in: MedlinePlus

Genomic structure and transcriptional regulation of the mouseOct4gene. The diagram represents ~24 kb of the genomic region surrounding the Oct4 gene [62]. The gene has five exons, depicted as blue boxes. The identified upstream regulatory regions include the promoter, proximal enhancer, and distal enhancer. The sizes of the regulatory elements are stretched to enhance clarity. The transcription factors bind to these regions, and are shown above within colored boxes; they either activate (green box) or repress (red box) transcription. HRE = hormone responsive element; Sp1 = GC-rich site recognized by the Sp1/Sp3 family of transcription factors. CR1, CR2, CR3, and CR4 are conserved regions (CRs) at the 5’ upstream region of the Oct4 gene.
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Fig2: Genomic structure and transcriptional regulation of the mouseOct4gene. The diagram represents ~24 kb of the genomic region surrounding the Oct4 gene [62]. The gene has five exons, depicted as blue boxes. The identified upstream regulatory regions include the promoter, proximal enhancer, and distal enhancer. The sizes of the regulatory elements are stretched to enhance clarity. The transcription factors bind to these regions, and are shown above within colored boxes; they either activate (green box) or repress (red box) transcription. HRE = hormone responsive element; Sp1 = GC-rich site recognized by the Sp1/Sp3 family of transcription factors. CR1, CR2, CR3, and CR4 are conserved regions (CRs) at the 5’ upstream region of the Oct4 gene.

Mentions: The upstream region of the transcriptional initiation site of the Oct4 gene contains three regulatory elements for gene transcription: the distal enhancer (DE), proximal enhancer (PE), and TATA-less proximal promoter (PP) [9] as illustrated in Figure 2. The two enhancers exhibit a differential activation pattern according to the developmental stage of the mouse embryo. The DE drives Oct4 expression in the ICM, ESCs, and PGCs, while the PE activates Oct4 expression in epiblast cells. Each enhancer contains multiple potential binding sites for transcription factors that can either activate or repress Oct4 expression. In addition, the methylation of these regions represses Oct4 expression in differentiated cells. Several positive and negative regulators bind to the Oct4 gene to regulate its expression. Of these, members of the orphan nuclear receptor superfamily, which can bind to Sp1 sites [54] and hormone response elements (HREs) in the PE and PP, are known to influence Oct4 expression. Positive regulators of Oct4 expression include Nr5a2[55], SF1 (Steroidogenic Factor-1), and RXR-β (Retinoid X Receptor-β, also known as Nr2b2) [56, 57]. Negative regulators include GCNF (Germ Cell Nuclear Factor) (also known as Nr6a1) [58], and COUF-TFI/II (Chicken Ovalbumin Upstream promoter-Transcription Factors- I/II), encoded by Nr2f1 and Nr2f2, respectively [59, 60]. The transcription factor TR2 can bind to the HRE of the Oct4 gene to either activate or repress Oct4 expression in P19 embryonal carcinoma (EC) stem cells and regulate the proliferation of the culture, based on whether there is SUMOylation on the Lys-238 of TR2 [61].Figure 2


Role of Oct4 in the early embryo development.

Wu G, Schöler HR - Cell Regen (Lond) (2014)

Genomic structure and transcriptional regulation of the mouseOct4gene. The diagram represents ~24 kb of the genomic region surrounding the Oct4 gene [62]. The gene has five exons, depicted as blue boxes. The identified upstream regulatory regions include the promoter, proximal enhancer, and distal enhancer. The sizes of the regulatory elements are stretched to enhance clarity. The transcription factors bind to these regions, and are shown above within colored boxes; they either activate (green box) or repress (red box) transcription. HRE = hormone responsive element; Sp1 = GC-rich site recognized by the Sp1/Sp3 family of transcription factors. CR1, CR2, CR3, and CR4 are conserved regions (CRs) at the 5’ upstream region of the Oct4 gene.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4230828&req=5

Fig2: Genomic structure and transcriptional regulation of the mouseOct4gene. The diagram represents ~24 kb of the genomic region surrounding the Oct4 gene [62]. The gene has five exons, depicted as blue boxes. The identified upstream regulatory regions include the promoter, proximal enhancer, and distal enhancer. The sizes of the regulatory elements are stretched to enhance clarity. The transcription factors bind to these regions, and are shown above within colored boxes; they either activate (green box) or repress (red box) transcription. HRE = hormone responsive element; Sp1 = GC-rich site recognized by the Sp1/Sp3 family of transcription factors. CR1, CR2, CR3, and CR4 are conserved regions (CRs) at the 5’ upstream region of the Oct4 gene.
Mentions: The upstream region of the transcriptional initiation site of the Oct4 gene contains three regulatory elements for gene transcription: the distal enhancer (DE), proximal enhancer (PE), and TATA-less proximal promoter (PP) [9] as illustrated in Figure 2. The two enhancers exhibit a differential activation pattern according to the developmental stage of the mouse embryo. The DE drives Oct4 expression in the ICM, ESCs, and PGCs, while the PE activates Oct4 expression in epiblast cells. Each enhancer contains multiple potential binding sites for transcription factors that can either activate or repress Oct4 expression. In addition, the methylation of these regions represses Oct4 expression in differentiated cells. Several positive and negative regulators bind to the Oct4 gene to regulate its expression. Of these, members of the orphan nuclear receptor superfamily, which can bind to Sp1 sites [54] and hormone response elements (HREs) in the PE and PP, are known to influence Oct4 expression. Positive regulators of Oct4 expression include Nr5a2[55], SF1 (Steroidogenic Factor-1), and RXR-β (Retinoid X Receptor-β, also known as Nr2b2) [56, 57]. Negative regulators include GCNF (Germ Cell Nuclear Factor) (also known as Nr6a1) [58], and COUF-TFI/II (Chicken Ovalbumin Upstream promoter-Transcription Factors- I/II), encoded by Nr2f1 and Nr2f2, respectively [59, 60]. The transcription factor TR2 can bind to the HRE of the Oct4 gene to either activate or repress Oct4 expression in P19 embryonal carcinoma (EC) stem cells and regulate the proliferation of the culture, based on whether there is SUMOylation on the Lys-238 of TR2 [61].Figure 2

Bottom Line: Oct4 of maternal origin is postulated to play critical role in defining totipotency and inducing pluripotency during embryonic development.These results indicate that Oct4 is not essential for the initiation of pluripotency, in contrast to its critical role in maintaining pluripotency.This conclusion is further supported by the formation of Oct4-GFP- and Nanog- expressing inner cell masses (ICMs) in embryos with complete inactivation of both maternal and zygotic Oct4 expression and the reprogramming of fibroblasts into fully pluripotent cells by Oct4-deficient oocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany.

ABSTRACT
Oct4 is a key component of the pluripotency regulatory network, and its reciprocal interaction with Cdx2 has been shown to be a determinant of either the self-renewal of embryonic stem cells (ESCs) or their differentiation into trophoblast. Oct4 of maternal origin is postulated to play critical role in defining totipotency and inducing pluripotency during embryonic development. However, the genetic elimination of maternal Oct4 using a Cre-lox approach in mouse revealed that the establishment of totipotency in maternal Oct4-depleted embryos was not affected, and that these embryos could complete full-term development without any obvious defect. These results indicate that Oct4 is not essential for the initiation of pluripotency, in contrast to its critical role in maintaining pluripotency. This conclusion is further supported by the formation of Oct4-GFP- and Nanog- expressing inner cell masses (ICMs) in embryos with complete inactivation of both maternal and zygotic Oct4 expression and the reprogramming of fibroblasts into fully pluripotent cells by Oct4-deficient oocytes.

No MeSH data available.


Related in: MedlinePlus