Stem cell-specific expression of Dax1 is conferred by STAT3 and Oct3/4 in embryonic stem cells

Sun, Chuanhai; Nakatake, Yuhki; Ura, Hiroki; Akagi, Tadayuki; Niwa, Hitoshi; Koide, Hiroshi; Yokota, Takashi

doi:10.1016/j.bbrc.2008.04.154

Cited by 37 publications

(50 citation statements)

References 28 publications

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“…we previously identified the nuclear hormone receptor Dax1 as a downstream target of STAT3 and Oct3/4 [8] and demonstrated its direct interactions with Oct3/4 [9]. Further, the nuclear localization of Dax1 is enhanced by Oct3/4, and the transcriptional activity of Oct3/4 is repressed by Dax1 [9].…”

Section: Introductionmentioning

confidence: 92%

Esrrb directly binds to Gata6 promoter and regulates its expression with Dax1 and Ncoa3

Uranishi

Akagi

Koide

et al. 2016

Biochemical and Biophysical Research Communications

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Estrogen-related receptor beta (Esrrb) is expressed in embryonic stem (ES) cells and is involved in self-renewal ability and pluripotency. Previously, we found that Dax1 is associated with Esrrb and represses its transcriptional activity. Further, the disruption of the Dax1-Esrrb interaction increases the expression of the extra-embryonic endoderm marker Gata6 in ES cells. Here, we investigated the influences of Esrrb and Dax1 on Gata6 expression. Esrrb overexpression in ES cells induced endogenous Gata6 mRNA and Gata6 promoter activity. In addition, the Gata6 promoter was found to contain the Esrrb recognition motifs ERRE1 and ERRE2, and the latter was the responsive element of Esrrb. Associations between ERRE2 and Esrrb were then confirmed by biotin DNA pulldown and chromatin immunoprecipitation assays. Subsequently, we showed that Esrrb activity at the Gata6 promoter was repressed by Dax1, and although Dax1 did not bind to ERRE2, it was associated with Esrrb, which directly binds to ERRE2. In addition, the transcriptional activity of Esrrb was enhanced by nuclear receptor co-activator 3 (Ncoa3), which has recently been shown to be a binding partner of Esrrb.Finally, we showed that Dax1 was associated with Ncoa3 and repressed its transcriptional activity. Taken together, the present study indicates that the Gata6 pCAGIP-Myc-Dax1, and pCAGIP-Myc-Dax1LTm, were generated as described previously [9,21]. The Ncoa3 coding region and its truncated mutants were amplified using polymerase chain reaction (PCR) before being cloned into expression vectors.The Gata6 gene promoter region (-0.9 kb) was amplified using PCR and was cloned into pGL4.10 (Promega, Madison, WI, USA) to produce the plasmid pGL4.10-Gata6P 0.9k. To construct the Esrrb-responsive element (ERRE)-mutant pGL4.10-Gata6P 0.9k plasmids, mutant ERRE1 or ERRE2 elements were generated using PCR with specific primers. PCR products were then cloned into pGL4.10 to produce pGL4.10-Gata6P 0.9k-ERRE1 mut and -ERRE2 mut vectors. All primer sequences are listed in Supplemental Table S1. 9Plasmids were introduced into cultured cells using Lipofectamine 2000 (Life Technologies, Grand Island, NY, USA). Two days after transfection, cells were treated with 1 μg/mL puromycin for 5-7 days, and RNA samples for RT-PCR were isolated and examined as described previously [21]. The cell extracts for the luciferase assays were prepared 48 h after transfection, and luciferase activity was measured using a luciferase assay kit (Promega) and an AB-2200 luminometer (ATTO, Tokyo, Japan). Biotin-labeled DNA pull-down and chromatin immunoprecipitation assaysBiotin-labeled DNA pull-down assays were performed as described previously [21]. Briefly, biotin-labeled oligonucleotides were incubated with A3-1 ES extracts or HEK293 cell extracts that had been transfected with pCAGIP-Myc-Dax1 and/or pCAGIP-Esrrb in the presence of streptavidin-agarose (Novagen, Darmstadt, Germany).Subsequently, non-labeled oligonucleotide (either wild-type or mutant) was added for competition assays at a ...

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Section: Introductionmentioning

confidence: 92%

Esrrb directly binds to Gata6 promoter and regulates its expression with Dax1 and Ncoa3

Uranishi

Akagi

Koide

et al. 2016

Biochemical and Biophysical Research Communications

Self Cite

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“…Lineage-specific progenitors are mostly tissue-specific stem cells that include mesenchymal stem cells (MSCs) for adipose, muscle, or bone; hematopoietic stem cells (HSCs) for blood or bone remodeling; and neural stem cells (NSCs) for the nervous system. Since ethical concerns limit the therapeutic applicability of ES cells in humans, autograft therapy using self-stem cells has been pursued to treat diverse categories of diseases including neurologic abbreviation abbreviation AR NR3C4 Adipogenesis (Singh et al, 2006;Gupta V et al, 2008) Myogenesis (Singh et al, 2003(Singh et al, , 2009) COUP-TFβ NR2F2 Adipogenesis (Xu et al, 2008;Li et al, 2009) Myogenesis (Bailey et al, 1998Lee et al, 2004) DAX-1 NR0B1 ES cell stemness (Wang et al, 2006;Kim et al, 2008;Sun et al, 2008;Xie et al, 2009) ERβ NR3A2 NSC differentiation (Wang et al, 2001;Brannvall et al, 2002;Kishi et al, 2005) ERRβ NR3B2 ES cell stemness (Zhou et al, 2007;van den Berg et al, 2008;Zhang X et al, 2008) Induce iPS cells (Gu et al, 2005a;Feng et al, 2009) GCNF NR6A1 ES cell differentiation (Gu et al, 2005b) Neuronal differentiation (Sattler et al, 2004;Chung et al, 2006;Akamatsu et al, 2009 (Wallen-Mackenzie et al, 2003;Perlmann and Wallen-Mackenzie, 2004;Blin et al, 2008;Jacobs et al, 2009) PPARδ NR1C2 Transdifferentiation (Holst et al, 2003Wang et al, 2004;Teunissen et al, 2007) PPARγ NR1C3 Adipogenesis (Tontonoz et al, 1994;Hu et al, 1995;Fu et al, 2005;Crossno et al, 2006;Yu et al, 2006;...…”

Section: Introductionmentioning

confidence: 99%

Nuclear receptor regulation of stemness and stem cell differentiation

Jeong

Mangelsdorf

2009

Exp Mol Med

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Stem cells include a diverse number of toti-, pluri-, and multi-potent cells that play important roles in cellular genesis and differentiation, tissue development, and organogenesis. Genetic regulation involving various transcription factors results in the self-renewal and differentiation properties of stem cells. The nuclear receptor (NR) superfamily is composed of 48 ligand-activated transcription factors involved in diverse physiological functions such as metabolism, development, and reproduction. Increasing evidence shows that certain NRs function in regulating stemness or differentiation of embryonic stem (ES) cells and tissue-specific adult stem cells. Here, we review the role of the NR superfamily in various aspects of stem cell biology, including their regulation of stemness, forward-and trans-differentiation events; reprogramming of terminally differentiated cells; and interspecies differences. These studies provide insights into the therapeutic potential of the NR superfamily in stem cell therapy and in treating stem cell-associated diseases (e.g., cancer stem cell).

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“…Similar to Klf4, Tbx3 is a fast responding mediator of LIF signaling that sustains the core pluripotency network through the direct activation of Nanog [11]. The orphan nuclear receptor Dax-1, which has been shown to be directly regulated by Nanog, Oct4, and Stat3 [31,45], functions as part of the extended core gene regulatory network that governs ESC fate where it interacts with other essential transcription factors to regulate a common set of genes involved in self-renewal and pluripotency [17,45,46]. Dax-1 has also demonstrated independent repressor function at differentiation genes [41].…”

Section: Results P/cip Expression Is Downregulated During Mesc Differmentioning

confidence: 99%

“…Doxycycline-inducible Flag-p/CIP clones were generated using the piggyBac transposition assay as previously described [31]. Following PCR amplification of Flag-p/CIP using attBmodified primer pairs, the product was cloned into pDONR221 using BP clonase (Invitrogen) according to manufacturer's instructions.…”

Section: Generation Of Doxycycline-inducible Flag-p/cip-ires-bgeo Clonesmentioning

confidence: 99%

Critical Components of the Pluripotency Network Are Targets for the p300/CBP Interacting Protein (p/CIP) in Embryonic Stem Cells

Chitilian

Thillainadesan

Manias³

et al. 2014

Stem Cells

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p/CIP, also known as steroid receptor coactivator 3 (SRC-3)/Nuclear Receptor Coactivator 3 (NCoA3), is a transcriptional coactivator that binds liganded nuclear hormone receptors, as well as other transcription factors, and facilitates transcription through direct recruitment of accessory factors. We have found that p/CIP is highly expressed in undifferentiated mouse embryonic stem cells (mESCs) and is downregulated during differentiation. siRNA-mediated knockdown of p/CIP decreased transcript levels of Nanog, but not Oct4 or Sox2. Microarray expression analysis showed that Klf4, Tbx3, and Dax-1 are significantly downregulated in mESCs when p/CIP is knocked down. Subsequent chromatin immunoprecipitation (ChIP) analysis demonstrated that Tbx3, Klf4, and Dax-1 are direct transcriptional targets of p/CIP. Using the piggyBac transposition system, a mouse ESC line that expresses Flag-p/CIP in a doxycycline-dependent manner was generated. p/CIP overexpression increased the level of target genes and promoted the formation of undifferentiated colonies. Collectively, these results indicate that p/CIP contributes to the maintenance of ESC pluripotency through direct regulation of essential pluripotency genes.

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Stem cell-specific expression of Dax1 is conferred by STAT3 and Oct3/4 in embryonic stem cells

Cited by 37 publications

References 28 publications

Esrrb directly binds to Gata6 promoter and regulates its expression with Dax1 and Ncoa3

Esrrb directly binds to Gata6 promoter and regulates its expression with Dax1 and Ncoa3

Nuclear receptor regulation of stemness and stem cell differentiation

Critical Components of the Pluripotency Network Are Targets for the p300/CBP Interacting Protein (p/CIP) in Embryonic Stem Cells

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