Identification of putative downstream genes of Oct‐3, a pluripotent cell‐specific transcription factor

Saijoh, Yukio; Fujii, Hideyuki; Meno, Chikara; Sato, Minoru; Hirota, Yuji; Nagamatsu, Shinya; Ikeda, Masako; Hamada, Hiroshi

doi:10.1046/j.1365-2443.1996.d01-237.x

Cited by 54 publications

(41 citation statements)

References 14 publications

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“…Oct-3/4 is known to either repress or activate target gene expression [53][54][55][56][57] and regulate the expression of multiple genes downstream [58]. Therefore, the lack of Oct-3/4 expression in SCNT embryos at the later stages of preimplantation development may inhibit their normal development to term.…”

Section: Discussionmentioning

confidence: 99%

Development of a Noninvasive Monitoring System for Evaluation of Oct-3/4 Promoter Status in Miniature Pig Somatic Cell Nuclear Transfer Embryos

Miyoshi

Mori

Mizobe

et al. 2009

Journal of Reproduction and Development

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Abstract. The present study was carried out to develop a noninvasive monitoring system for evaluation of Oct-3/4 promoter gene status in miniature pig somatic cell nuclear transfer (SCNT) embryos during in vitro development. Miniature pig fetal fibroblasts (MPFFs) were transfected with a gene construct consisting of two expression units, a mouse Oct-3/4 promoter-driven enhanced green fluorescent protein (EGFP) gene (EGFP expression only detected in Oct-3/4-expressing cells) and a neomycin resistance gene. After neomycin selection, MPFFs that did not express EGFP were fused with enucleated pig oocytes, cultured in vitro and assessed for EGFP expression. EGFP expression was detectable in all morulae (at 4-6 days of culture) and 50.0% of blastocysts (at 5-6 days of culture), whereas none of the 1-cell to 16-cell embryos at 1-5 days of culture expressed EGFP. On the other hand, EGFP expression was not maintained in all blastocysts at 7 days of culture. The reactivity with anti-Oct-3/4 antibodies also peaked from the morula to blastocyst stages at 5 days of culture. The results showed that reactivation of the Oct-3/4 promoter gene of donor nuclei occurs in the morula to blastocyst stages at 4-6 days after SCNT and that this noninvasive monitoring system using Oct-3/4 promoter-driven EGFP gene would be useful for evaluation of the reprogramming status of donor nuclei. Key words: Enhanced green fluorescent protein, In vitro development, Nuclear transfer, Oct-3/4 promoter, Reprogramming (J. Reprod. Dev. 55: [661][662][663][664][665][666][667][668][669] 2009) uccessful production of cloned animals using somatic cell nuclear transfer (SCNT) has been reported in several mammalian species [1][2][3][4][5][6][7][8][9][10][11][12]. However, the low cloning efficiency associated with development of SCNT embryos to offspring remains the major obstacle to widespread use of this technology in a number of animal science and biomedical applications. A method for evaluating the developmental ability of SCNT embryos before being transferred into recipient females should be explored to optimize the procedures of SCNT and overcome the low cloning efficiency. Evaluation of the in vitro developmental ability of an SCNT embryo to the blastocyst stage would be considered one of the methods for predicting its in vivo development, but it has been found that this does not often assure successful development to term of SCNT embryos [13]. After SCNT, the gene expression pattern in somatic cells is reprogrammed to mimic that in preimplantation embryos [14]. However, there is a difference in gene expression pattern between SCNT embryos and in vitro-fertilized embryos, suggesting that the low efficiency of SCNT is associated with incomplete reprogramming in the donor nuclei transferred into recipient oocytes [15]. Therefore, evaluation of the reprogramming level in the donor nuclei appears to be most essential for predicting the in vivo developmental ability of SCNT embryos.Oct-3/4 is a transcription factor of the Pit-Oct-Unc family [16,17], and...

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Section: Discussionmentioning

confidence: 99%

Development of a Noninvasive Monitoring System for Evaluation of Oct-3/4 Promoter Status in Miniature Pig Somatic Cell Nuclear Transfer Embryos

Miyoshi

Mori

Mizobe

et al. 2009

Journal of Reproduction and Development

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“…It was recently shown that LSD1 binds to a proximal enhancer of Lefty1 and regulates Lefty1 expression in mES cells by controlling the methylation status of H3K4 (14,44). Lefty1 encodes a transforming growth factor beta (TGF␤) superfamily protein (45) that antagonizes the functions of Activin and Nodal and is essential in the establishment of left-right asymmetry of the embryo (46,47). It has been suggested that the function of Lefty1 in stem cells is to protect them from the action of developmental inducers (48).…”

Section: ␤-Catenin Chromatin Interactome In Mouse Embryonic Stem Cellsmentioning

confidence: 99%

Wnt3a-dependent and -independent Protein Interaction Networks of Chromatin-bound β-catenin in Mouse Embryonic Stem Cells

Yakulov

Raggioli

Franz

et al. 2013

Molecular & Cellular Proteomics

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Canonical Wnt signaling is repeatedly used during development to control cell fate, and it is often implicated in human cancer. ␤-catenin, the effector of Wnt signaling, has a dual function in the cell and is involved in both cell adhesion and transcription. Nuclear ␤-catenin controls transcription through association with transcription factors of the TCF family and the recruitment of epigenetic modifiers. In this study, we used a strategy combining the genetic manipulation of mouse embryonic stem cells with affinity purification and quantitative mass spectroscopy utilizing stable isotope labeling with amino acids in cell culture to study the interactome of chromatin-bound ␤-catenin with and without Wnt3a stimulation. We uncovered previously unknown interactions of ␤-catenin with transcription factors and chromatin-modifying complexes. The canonical Wnt signaling pathway plays multiple roles in development and is often dysregulated in human cancers (1). The key event in the canonical Wnt signaling is the regulation of ␤-catenin. Under normal conditions, the levels of ␤-catenin are low as a result of its phosphorylation by the destruction complex and subsequent ubiquitination and degradation by the proteasome (1). The destruction complex contains the scaffold proteins APC and Axin1, protein phosphatase 2a, and the kinases glycogen synthase kinase (GSK)-3␤ and casein kinase I alpha. Upon binding of Wnt ligands to the receptors Frizzled and LRP5/6, the destruction complex is turned off via translocation to the plasma membrane, where it binds Dishevelled. Thus, ␤-catenin is stabilized, translocates to the nucleus, and associates with TCF factors and with various proteins that are implicated in chromatin structure and RNA polymerase II regulation (1, 2).The interactions of ␤-catenin with chromatin effector proteins are concentrated at the C-terminal domain of ␤-catenin, as shown for the histone acetyltransferases CBP and p300, the histone methyltransferase MLL, the nucleosome repositioning SWI/SNF family member protein Brg1, the Mediator component MED12, and the BCL-9/Pygo complex, which has the ability to bind methylated H3K4 (2). It is not probable that all these bulky multiprotein assemblies simultaneously occupy the C-terminal domain of ␤-catenin. Other transcription factors use the same repertoire of co-activators via sequential or cycling recruitment (3). It is likely that ␤-catenin serves as a platform which orchestrates the sequential recruitment of chromatin remodeling factors in a stimulus-dependent manner.In mES 1 cells, the epigenetic regulation of gene expression has been shown to take place at the levels of DNA methylation, histone modification, nucleosome packaging and rearrangement, and higher order chromatin organization (4). Unique to key developmental genes in mES cells are bivalent chromatin domains with both activating and repressing marks, which contribute to the pluripotency potential of mES cells (5). Although Wnt/␤-catenin signaling has been shown to play a role in the self-renewal and plurip...

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“…In addition, Oct4 can act on a subset of target genes by binding to alternative A/T-rich sites (Saijoh et al, 1996). Expression of Oct4 occurs in the unfertilized egg and the early embryo prior to segregation of the ICM from the trophectoderm (Pesce and Scholer, 2001).…”

Section: Intrinsic Determinants Of Es Cell Self-renewalmentioning

confidence: 99%

Self-renewal of teratocarcinoma and embryonic stem cells

2004

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Pluripotent stem cells derived from preimplantation embryos, primordial germ cells or teratocarcinomas are currently unique in undergoing prolonged symmetrical self-renewal in culture. For mouse embryonic stem (ES) cells, self-renewal is dependent on signals from the cytokine leukaemia inhibitory factor (LIF) and from either serum or bone morphogenetic proteins (BMPs). In addition to the extrinsic regulation of gene expression, intrinsic transcriptional determinants are also required for maintenance of the undifferentiated state. These include Oct4, a member of the POU family of homeodomain proteins and a second recently identified homeodomain protein, Nanog. When overexpressed, Nanog allows ES cells to self-renew in the absence of the otherwise obligatory LIF and BMP signals. Although Nanog can act independent of the LIF signal, a contribution of both pathways provides maximal self-renewal efficiency. Nanog function also requires Oct4. Here, we review recent progress in ES cell self-renewal, relate this to the biology of teratocarcinomas and offer testable hypotheses to expose the mechanics of ES cell self-renewal.

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Identification of putative downstream genes of Oct‐3, a pluripotent cell‐specific transcription factor

Abstract: Background: Oct-3, a pluripotent cell-specific POU transcription factor, appears to be a key regulator in pluripotential early embryonic cells and germ cells. In order to study how pluripotency is maintained, it is essential to know what genes are regulated by Oct-3.

Cited by 54 publications

References 14 publications

Development of a Noninvasive Monitoring System for Evaluation of Oct-3/4 Promoter Status in Miniature Pig Somatic Cell Nuclear Transfer Embryos

Development of a Noninvasive Monitoring System for Evaluation of Oct-3/4 Promoter Status in Miniature Pig Somatic Cell Nuclear Transfer Embryos

Wnt3a-dependent and -independent Protein Interaction Networks of Chromatin-bound β-catenin in Mouse Embryonic Stem Cells

Self-renewal of teratocarcinoma and embryonic stem cells

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