5'-flanking motifs control cell-specific expression of trefoil factor genes (TFF).

Beck, Steve; Sommer, Patricia; Blin, Nikolaus; Gött, Peter

doi:10.3892/ijmm.2.3.353

Cited by 19 publications

(46 citation statements)

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“…The plasmid pCEFL-HA containing the neomycin resistance gene was provided by S. Emami (Institut National de la Santé et de la Recherche Médicale, Unité 482, Paris, France). The plasmid named p800 containing the first 800 bp of TFF3 promoter cloned into HindIII and SacI sites of plasmid pGL3-basic (positions Ϫ867 to ϩ 66), the TFF3.d1 plasmid containing the first 495 bp of TFF3 promoter cloned into the HindIII and KpnI sites of pGL3-basic, and the pUC 18 4.10 plasmid containing 10 kb of hTFF3 genomic DNA have been previously described (27). All oligonucleotides used for RT-PCR and EMSA analysis were custom-synthesized by Invitrogen (Cergy-Pontoise, France).…”

Section: Methodsmentioning

confidence: 99%

“…The proximal part of the TFF3 promoter does not contain canonical STAT6 binding elements (TTCnnnnGAA), but five noncanonical binding sites (TTnnnnnnAA) were identified. Luciferase reporter constructs containing up to 800 bp of TFF3 promoter have been described previously by one of us (27). They were transiently transfected into intestinal cells.…”

Section: Mechanism Of the Il-4-and Il-13-mediated Up-regulation Of Tfmentioning

confidence: 99%

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IL-4 and IL-13 Up-Regulate Intestinal Trefoil Factor Expression: Requirement for STAT6 and De Novo Protein Synthesis

Blanchard

Durual

Estienne

et al. 2004

The Journal of Immunology

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The development of intestinal goblet cell hyperplasia/hypertrophy during nematode infection involves the Th2 cytokines IL-4 and IL-13 via STAT6 activation. This is thought to play an important role in host protective immunity against the infection. In this study we demonstrate that IL-4 and IL-13 up-regulate the specific goblet cell product trefoil factor-3 (TFF3) from the mucus-producing HT-29 CL.16E and HT-29 cells selected by adaptation to methotrexate. Up-regulation of TFF3 mRNA and protein levels occurred in a time- and dose-dependent fashion and was accompanied by up-regulation of the goblet cell product mucin 2 (MUC2). Addition of actinomycin D before IL-4/IL-13 stimulation led to decreases in TFF3 mRNA levels similar to those observed in controls without IL-4/IL-13. Furthermore, IL-4-mediated increased TFF3 transcription required de novo protein synthesis. Stable transfection of HT-29 CL.16E cells with a truncated dominant-negative form of STAT6 produced a cell line that was unresponsive to IL-4/IL-13. Although only one consensus STAT6 binding site is contained in the TFF3 gene, located in the intron 1, it did not operate as an enhancer in the context of an SV40 promoter/luciferase construct. Thus, STAT6 activation mediates a transcriptional enhancement of TFF3 by induction of de novo synthesized protein in goblet cells.

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Section: Methodsmentioning

confidence: 99%

Section: Mechanism Of the Il-4-and Il-13-mediated Up-regulation Of Tfmentioning

confidence: 99%

IL-4 and IL-13 Up-Regulate Intestinal Trefoil Factor Expression: Requirement for STAT6 and De Novo Protein Synthesis

Blanchard

Durual

Estienne

et al. 2004

The Journal of Immunology

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“…A site-directed mutagenesis study demonstrated that the Motif III and Motif IV contributed positively to transcriptional regulation of human TFF1 gene. 20) In this regard, the roles of HNF3/FKH proteins which recognized human Motif IV and triggered transcription of the TFF1 reporter gene 21) are of interest from the viewpoints of TFF1 induction upon injury, inflammation and tumor development 21,22) as well as tissue-specific TFF1 expression. However, it should also be mensioned that DNA methylation of the promoter region of TFF1 gene is another important factor for gene regulation associated with carcinogenesis.…”

Section: Fig 6 Analysis Of the Promoter Region By Means Of The Repomentioning

confidence: 99%

Characterization of the Mouse TFF1 (pS2) Gene Promoter Region.

Terada

Sakagami

Tabuchi

et al. 2001

Biological & Pharmaceutical Bulletin

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Trefoil peptides (TFFs) are small and stable molecules secreted by the mammalian gastrointestinal tract.1) The term "trefoil", meaning three leaves, is derived from their three intrachain loops (trefoil domain) that are maintained by disulfide bonds. Three family members are found in mammals: TFF1/pS2 and TFF3/ITF contain one trefoil domain, whereas TFF2/SP has two domains.2) It is suggested that the TFFs could be involved in protection and repair of the gastrointestinal tract through stimulation of cell migration and mucus polymerization. Actually, mice lacking TFF3 exhibited impaired mucosal healing and died from extensive colitis after oral administration of dextran sulfate.3) Furthermore, loss of TFF1 induced severe hyperplasia and dysplasia of the gastric mucosa, and the development of adenomas and carcinomas. 4)The results suggest that TFF1 is essential for normal differentiation of the gastric mucosa and that it functions as a tumor suppressor.The three TFFs exhibit strict tissue-specific expression patterns: TFF1 in stomach, TFF2 in stomach and duodenum, and TFF3 in small intestine and colon.2) We are interested in the gene regulation of TFF1 from the viewpoint of stomachspecific transcription, as our previous studies focused on the genes specifically expressed in stomach, such as those of the gastric proton pump, 5,6) intrinsic factor, 7) and H 2 receptor. 8) In this study, we cloned the mouse TFF1 gene 5Ј-upstream sequence, and identified the enhancer and silencer regions by means of a reporter gene assay. Furthermore, significance of the sequence motifs in the upstream regions are discussed in comparison with those in the human gene. MATERIALS AND METHODS Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)Total RNA was prepared from tissues of a 6-weekold male ddY mouse by the guanidine thiocyanate-CsCl method.9) cDNA was synthesized from total RNA (8 mg) with a First-Strand cDNA Synthesis Kit (Amersham-PharmaciaBiotech) and an oligo d(T)12-18 primer, and then subjected to PCR 10) to amplify specific nucleotide sequences for the three TFFs. The pairs of PCR primers used for TFF1 (S29 and S30), TFF2 (S26 and S27) and TFF3 (S3 and S4) are shown in Table 1. The PCR conditions were: preheating (94°C, 3 min), followed by 35 cycles of denaturation (94°C, 0.5 min), annealing (54°C for TFF1, 58°C for TFF2, or 62°C for TFF3, 0.5 min), and extension (72°C, 0.5 min). The 2nd PCR was carried out for TFF3 (54°C annealing). The products were analyzed by agarose gel electrophoresis [1.0% (w/v) agarose (TaKaRa L03) in TAE-buffer 9) ], and visualized by ethidium bromide staining.Total cellular RNA was prepared from GSM10 cells 11,12) as above and then PCR analysis was carried out. The PCR conditions were essentially the same as for tissues except that the annealing temperature and cycle number for the three TFFs were 61°C and 40 cycles, respectively. The GSM10 cells, the generous gift of Daiichi Pharmaceutical Co., Ltd., were cultured in Dulbecco's modified Eagle medium/F12 medium (GIBCO BRL) containing 10% (v/v)...

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“…26 Deletion of Motif III or Motif IV was also found to significantly lessen the transcription of the TFF1 gene. 26 This evidence indicates that these motifs may be involved in the regulation of TFF1 expression in the stomach. Beck et al 27 investigated the regulation of TFF1 expression further by focusing on HNF-3 transcription factors.…”

mentioning

confidence: 94%

“…26 Motif II (nucleotide )400 to )384 from the TATA box of the human TFF1 gene) was found to be similar to the binding site for heat shock factor HSH-2, and TFF1 reporter gene transcription was decreased even further when regions covering both Motif I and Motif II were deleted. 26 Motif III (nucleotides )40 to )30…”

mentioning

confidence: 98%

Review article: regulation of TFF1 (pS2) expression in gastric epithelial cells

Fujii

Shimada

Koike

et al. 2006

Aliment Pharmacol Ther

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SUMMARYTrefoil factor family (TFF) is a group of small peptides secreted by gastrointestinal epithelial cells.Among three known TFF peptides, TFF1 (formerly pS2) is expressed at a high level in gastric epithelial cells and plays an essential and critical role in maintaining the integrity of the gastric mucosa. Recent evidence also suggests that TFF1 acts as a tumour suppressor gene in the stomach.TFF1 was originally discovered as an oestrogen-inducible gene in MCF-7 breast cancer cells, and its expression is dependent on oestrogen in MCF-7 and other hormone-dependent breast cancer cells. Although gastric epithelial cells express oestrogen receptors (ERs), gastric TFF1 expression appears to be independent of oestrogen signalling. Instead, several cis-regulatory elements are involved in the regulation of gastric TFF1 expression and balanced signalling from gp130, a common IL-6 family coreceptor, has been shown to be necessary for the proper expression of TFF1 in the stomach.Epigenetic regulation, such as DNA methylation in the promoter region of the TFF1 gene, may be also important for tissue-specific expression of TFF1 in the stomach. However, further studies are still needed to fully understand the detailed regulatory mechanisms of TFF1 expression in gastric epithelial cells.

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5'-flanking motifs control cell-specific expression of trefoil factor genes (TFF).

Cited by 19 publications

References 0 publications

IL-4 and IL-13 Up-Regulate Intestinal Trefoil Factor Expression: Requirement for STAT6 and De Novo Protein Synthesis

IL-4 and IL-13 Up-Regulate Intestinal Trefoil Factor Expression: Requirement for STAT6 and De Novo Protein Synthesis

Characterization of the Mouse TFF1 (pS2) Gene Promoter Region.

Review article: regulation of TFF1 (pS2) expression in gastric epithelial cells

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