scholarly journals Nuclear Factor 1 and T-Cell Factor/LEF Recognition Elements Regulate Pitx2 Transcription in Pituitary Development

2007 ◽  
Vol 27 (16) ◽  
pp. 5765-5775 ◽  
Author(s):  
Di Ai ◽  
Jun Wang ◽  
Melanie Amen ◽  
Mei-Fang Lu ◽  
Brad A. Amendt ◽  
...  
Keyword(s):  
T Cell ◽  
Homeobox Gene ◽  
Nuclear Factor ◽  
T Cell Factor ◽  
Pituitary Development ◽  
Oral Ectoderm ◽  
Lacz Activity ◽  
Nuclear Factor 1 ◽  
Transgenic Embryos

ABSTRACT Pitx2, a paired-related homeobox gene that is mutated in Rieger syndrome I, is the earliest known marker of oral ectoderm. Pitx2 was previously shown to be required for tooth, palate, and pituitary development in mice; however, the mechanisms regulating Pitx2 transcription in the oral ectoderm are poorly understood. Here we used an in vivo transgenic approach to investigate the mechanisms regulating Pitx2 transcription. We identified a 7-kb fragment that directs LacZ expression in oral ectoderm and in many of its derivatives. Deletion analysis of transgenic embryos reduced this fragment to a 520-bp region that directed LacZ activity to Rathke's pouch. A comparison of the mouse and human sequences revealed a conserved nuclear factor 1 (NF-1) recognition element near a consensus T-cell factor (TCF)/LEF binding site. The mutation of either site individually abolished LacZ activity in transgenic embryos, identifying Pitx2 as a direct target of Wnt signaling in pituitary development. These findings uncover a requirement for NF-1 and TCF factors in Pitx2 transcriptional regulation in the pituitary and provide insight into the mechanisms controlling region-specific transcription in the oral ectoderm and its derivatives.

scholarly journals Differential Effects of Hepatocyte Nuclear Factor 4α Isoforms on Tumor Growth and T-Cell Factor 4/AP-1 Interactions in Human Colorectal Cancer Cells

2015 ◽  
Vol 35 (20) ◽  
pp. 3471-3490 ◽  
Author(s):  
Linh M. Vuong ◽  
Karthikeyani Chellappa ◽  
Joseph M. Dhahbi ◽  
Jonathan R. Deans ◽  
Bin Fang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
T Cell ◽  
Tumor Growth ◽  
Hct116 Cell ◽  
Xenograft Model ◽  
Global Changes ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
T Cell Factor ◽  
Hepatocyte Nuclear Factor 4Α

The nuclear receptor hepatocyte nuclear factor 4α (HNF4α) is tumor suppressive in the liver but amplified in colon cancer, suggesting that it also might be oncogenic. To investigate whether this discrepancy is due to different HNF4α isoforms derived from its two promoters (P1 and P2), we generated Tet-On-inducible human colon cancer (HCT116) cell lines that express either the P1-driven (HNF4α2) or P2-driven (HNF4α8) isoform and analyzed them for tumor growth and global changes in gene expression (transcriptome sequencing [RNA-seq] and chromatin immunoprecipitation sequencing [ChIP-seq]). The results show that while HNF4α2 acts as a tumor suppressor in the HCT116 tumor xenograft model, HNF4α8 does not. Each isoform regulates the expression of distinct sets of genes and recruits, colocalizes, and competes in a distinct fashion with the Wnt/β-catenin mediator T-cell factor 4 (TCF4) at CTTTG motifs as well as at AP-1 motifs (TGAXTCA). Protein binding microarrays (PBMs) show that HNF4α and TCF4 share some but not all binding motifs and that single nucleotide polymorphisms (SNPs) in sites bound by both HNF4α and TCF4 can alter binding affinityin vitro, suggesting that they could play a role in cancer susceptibilityin vivo. Thus, the HNF4α isoforms play distinct roles in colon cancer, which could be due to differential interactions with the Wnt/β-catenin/TCF4 and AP-1 pathways.

scholarly journals Chromatin-Mediated Restriction of Nuclear Factor 1/CTF Binding in a Repressed and Hormone-Activated Promoter In Vivo

2004 ◽  
Vol 24 (7) ◽  
pp. 3036-3047 ◽  
Author(s):  
Sergey Belikov ◽  
Carolina Åstrand ◽  
Per-Henrik Holmqvist ◽  
Örjan Wrange
Keyword(s):  
Dna Binding ◽  
Chromatin Remodeling ◽  
Gene Networks ◽  
Fold Increase ◽  
Micrococcal Nuclease ◽  
Specific Gene ◽  
Nuclear Factor ◽  
Mmtv Promoter ◽  
Nuclear Factor 1

ABSTRACT Mouse mammary tumor virus (MMTV) promoter-driven transcription is induced by glucocorticoid hormone via binding of the glucocorticoid receptor (GR). The MMTV promoter also harbors a binding site for nuclear factor 1 (NF1). NF1 and GR were expressed in Xenopus oocytes; this revealed GR-NF1 cooperativity both in terms of DNA binding and chromatin remodeling but not transcription. A fraction of NF1 sites were occupied in a hormone-dependent fashion, but a significant and NF1 concentration-dependent fraction were constitutively bound. Activation of the MMTV promoter resulted in an ∼50-fold increase in the NF1 accessibility for its DNA site. The hormone-dependent component of NF1 binding was dissociated by addition of a GR antagonist; however, the antagonist RU486, which supports partial GR-DNA binding, also maintained partial NF1 binding. Hence GR-NF1 cooperativity is independent of agonist-driven chromatin remodeling. NF1 induced the formation of a micrococcal-nuclease-resistant protein-DNA complex containing the DNA segment from −185 to −55, the MMTV enhanceosome. Coexpression of NF1 and Oct1 resulted in a significant stimulation of hormone-induced MMTV transcription and also in increased basal transcription. We propose that hormone-independent NF1 binding may be involved in maintaining transcriptional competence and establishment of tissue-specific gene networks.

A T-CELL FACTOR THAT MEASURES INTERMEDIATE STEPS IN IN VIVO IMMUNE RESPONSES

1979 ◽  
Vol 332 (1 Subcellular F) ◽  
pp. 460-463
Author(s):  
Myron A. Leon ◽  
Tuan-Huey Kuo
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Factor

scholarly journals Combined Deficiency of p50 and cRel in CD4+ T Cells Reveals an Essential Requirement for Nuclear Factor κB in Regulating Mature T Cell Survival and In Vivo Function

2003 ◽  
Vol 197 (7) ◽  
pp. 861-874 ◽  
Author(s):  
Ye Zheng ◽  
Monika Vig ◽  
Jesse Lyons ◽  
Luk Van Parijs ◽  
Amer A. Beg
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Survival ◽  
Cd4 T Cells ◽  
Cell Function ◽  
Nuclear Factor ◽  
T Cell Function ◽  
T Cell Survival

Signaling pathways involved in regulating T cell proliferation and survival are not well understood. Here we have investigated a possible role of the nuclear factor (NF)-κB pathway in regulating mature T cell function by using CD4+ T cells from p50−/− cRel−/− mice, which exhibit virtually no inducible κB site binding activity. Studies with these mice indicate an essential role of T cell receptor (TCR)-induced NF-κB in regulating interleukin (IL)-2 expression, cell cycle entry, and survival of T cells. Our results further indicate that NF-κB regulates TCR-induced expression of antiapoptotic Bcl-2 family members. Strikingly, retroviral transduction of CD4+ T cells with the NF-κB–inducing IκB kinase β showed that NF-κB activation is not only necessary but also sufficient for T cell survival. In contrast, our results indicate a lack of involvement of NF-κB in both IL-2 and Akt-induced survival pathways. In vivo, p50−/− cRel−/− mice showed impaired superantigen-induced T cell responses as well as decreased numbers of effector/memory and regulatory CD4+ T cells. These findings provide the first demonstration of a role for NF-κB proteins in regulating T cell function in vivo and establish a critically important function of NF-κB in TCR-induced regulation of survival.

T cell factor which can replace T cells in vivo

Nature ◽  
1974 ◽  
Vol 248 (5445) ◽  
pp. 234-236 ◽  
Author(s):  
M. J. TAUSSIG
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Factor

scholarly journals T Cell Factor 4 Is a Pro-catabolic and Apoptotic Factor in Human Articular Chondrocytes by Potentiating Nuclear Factor κB Signaling

2013 ◽  
Vol 288 (24) ◽  
pp. 17552-17558 ◽  
Author(s):  
Bin Ma ◽  
Leilei Zhong ◽  
Clemens A. van Blitterswijk ◽  
Janine N. Post ◽  
Marcel Karperien
Keyword(s):  
T Cell ◽  
Articular Chondrocytes ◽  
Nuclear Factor Κb ◽  
Human Articular Chondrocytes ◽  
Nuclear Factor ◽  
T Cell Factor

scholarly journals Chromatin-Mediated Restriction of Nuclear Factor 1/CTF Binding in a Repressed and Hormone-Activated Promoter In Vivo

2004 ◽  
Vol 24 (12) ◽  
pp. 5636-5636
Author(s):  
Sergey Belikov ◽  
Carolina Åstrand ◽  
Per-Henrik Holmqvist ◽  
Örjan Wrange
Keyword(s):  
Nuclear Factor ◽  
Nuclear Factor 1

scholarly journals Properties of antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. I. In vivo activity and immunochemical characterization.

1975 ◽  
Vol 142 (5) ◽  
pp. 1241-1253 ◽  
Author(s):  
T Takemori ◽  
T Tada
Keyword(s):  
T Cell ◽  
Antibody Response ◽  
Gel Filtration ◽  
Donor Strain ◽  
Spleen Cells ◽  
Protein Antigens ◽  
Igg Antibody ◽  
Suppressor Factor ◽  
T Cell Factor

An antigen-specific suppressive T-cell factor was extracted from physically disrupted thymocytes and spleen cells of mice that had been immunized with soluble protein antigens. The factor, when inoculated into syngeneic normal mice, could induce a significant suppression of IgG antibody response against a hapten coupled to the carrier protein by which the donor of the suppressor factor was immunized. The suppressor factor was found only effective in suppressing the antibody response of syngeneic or H-2 histocompatible recipients. The suppressive T-cell factor was removed by absorption with immunoadsorbent composed of the relevant antigen, but not with any of those of anti-immunoglobulin antibodies. The factor was successfully removed by alloantibodies with specificity for the K end (H-2K, I-A and I-B) of the H-2 complex of the donor strain, but not by those for the D end (I-C, SsSlp, and H-2D). The activity was removed by absorption with a heterologous antithymocyte serum. The mol wt of the suppression T-cell factor was between 35,000 and 60,000 as determined by Sephadex G-200 gel filtration. The suppressive T-cell factor was found to be a heat-liable protein.

scholarly journals Pseudopregnancy induces the expression of hepatocyte nuclear factor-1β and its target gene aminopeptidase N in rabbit endometrium via the epithelial promoter

1995 ◽  
Vol 312 (1) ◽  
pp. 31-37 ◽  
Author(s):  
J Olsen ◽  
I Classen-Linke ◽  
H Sjöström ◽  
O Norén
Keyword(s):  
Transcription Factor ◽  
Binding Proteins ◽  
Experimental Manipulation ◽  
Nuclear Hormone Receptor ◽  
Aminopeptidase N ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Parallel Increase ◽  
Nuclear Factor 1

The rabbit endometrium is an excellent model system allowing experimental manipulation of aminopeptidase N (APN) mRNA expression in vivo. By RNase mapping and sequencing of cloned PCR-amplified primer-extended RNA, it was demonstrated that endometrial APN expression is directed by the epithelial APN promoter and is increased in human-choriogonadotropin-induced pseudopregnancy. Cloning and sequencing of the rabbit APN epithelial promoter revealed conservation of the upstream footprint (UF), hepatocyte nuclear factor-1 (HNF1) and Sp1 elements known to be present in the pig and human promoters as well. The pseudopregnancy-induced APN expression was found to be accompanied by a parallel increase in the level of the transcription factor HNF1 beta, whereas a much smaller increase in Sp1 and UF-binding proteins was observed. This indicates that HNF1 beta acts as a switch triggering the pregnancy-induced APN expression. The sequence of the UF element suggests members of the nuclear hormone-receptor superfamily as possible UF-binding proteins, and competition experiments suggest that the chicken ovalbumin upstream promoter transcription factor functions as such in the rabbit endometrium.

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