Identification of two silencers flanking an AP-1 enhancer in the vimentin promoter

Klundert, Francy A. J. M. van de; Eldik, G.J. van; Pieper, Frank; Jansen, Hans J.; Bloemendal, H.

doi:10.1016/0378-1119(92)90223-c

Cited by 31 publications

(11 citation statements)

References 36 publications

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“…Recently, van de Klundert et al (52) identified two functional SEs in the hamster vimentin gene, Sill (-741 to -712) and Sil2 (-655 to -635). Sil2 has a limited sequence similarity to SE3 (8 of 21) and human vimentin (7 of 16) at -811 to -796, which is not within the functional 19-bp negative element delineated by Salvetti et al (41).…”

Section: Resultsmentioning

confidence: 99%

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Multiple silencer elements are involved in regulating the chicken vimentin gene.

Garzon

Zehner

1994

Mol. Cell. Biol.

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Vimentin, a member of the intermediate filament protein family, exhibits tissue-as well as developmentspecific expression. Transcription factors that are involved in expression of the chicken vimentin gene have been described and include a cis-acting silencer element (SE3) that is involved in the down-regulation of this gene (F. X. Farrell, C. M. Sax, and Z. E. Zehner, Mol. Cell. Biol. 10:2349Biol. 10: -2358Biol. 10: , 1990. In this study, we report the identification of two additional silencer elements (SE1 and SE2). We show by transfection analysis that all three silencer elements are functionally active and that optimal silencing occurs when multiple (at least two) silencer elements are present. In addition, the previously identified SE3 can be divided into three subregions, each of which is moderately active alone. By (4,22,28,39). For example, induction of vimentin expression has been linked to serum, platelet-derived growth factor, and phorbol esters (23,38,39), in addition to more general transcription factors such as SP-1 (8). In the chicken vimentin gene, differential vimentin expression has been shown to involve several cis elements and trans factors (43-45, 50, 53, 54). However, one of the more interesting aspects of vimentin gene regulation is that it is also down-regulated during development. The primary locale of this negative regulation was determined to be a 40-bp silencer element (SE3) located at -607 to -567 from the start site of transcription (14,44). This element was shown to bind a factor of 95 kDa (14), the silencer element protein (SEP). Upon further analysis, SE3 was observed to contain some sequence similarity to the octamer-binding sequence (4) which has been observed in a negative element in the human c-myc gene (51). However, the data suggest that SEP is a different factor.One important conclusion from this study was that while SE3 could act in a position-and orientation-independent manner, a single copy yielded only a partial reduction in transcription within the native context of the gene and 36% compared with that of the heterologous herpes simplex virus (HSV) thymidine kinase (tk) promoter (ptkCAT) (14). In fact, multiple SE copies (more than two) were (14). Here, we show by transfection analyses that there are at least three SEs active within the chicken vimentin gene. Moreover, all three elements appear to bind the same silencer protein (95 kDa) as measured by gel mobility shift assays (GMSAs), UV cross-linking experiments, and Southwestern (DNA-protein) blots. Transfection data suggest that for complete repression of transcription, multiple (at least two) SE copies are required.The presence of multiple negative elements is not unique to the chicken vimentin gene. Since our initial report, multiple negative elements have also been found in the chicken lysozyme (2, 3), rat glutathione P-transferase (19), human 8-globin (9), interleukin-4 (30), collagen II (42), and hamster (52) and human (41) vimentin genes. Possible mechanistic models are presented to account for the nee...

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Section: Resultsmentioning

confidence: 99%

“…Since our initial report, multiple negative elements have also been found in the chicken lysozyme (2, 3), rat glutathione P-transferase (19), human 8-globin (9), interleukin-4 (30), collagen II (42), and hamster (52) and human (41) vimentin genes. Possible mechanistic models are presented to account for the need for multiple SEs.…”

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confidence: 99%

Multiple silencer elements are involved in regulating the chicken vimentin gene.

Garzon

Zehner

1994

Mol. Cell. Biol.

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“…Silencer activity has been implicated in the regulation of the vimentin gene, another intermediate filament gene (12,17,50,59). However, the expression of vimentin in F9 cells, the absence of apparent sequence homology to the K18 silencers, and the activity of the vimentin silencers in several somatic cell types suggest that the silencer elements of the two types of intermediate filament genes are probably mediated by different factors.…”

Section: Discussionmentioning

confidence: 99%

AP-1, ETS, and transcriptional silencers regulate retinoic acid-dependent induction of keratin 18 in embryonic cells.

Pankov¹,

Neznanov²,

Umezawa³

et al. 1994

Mol. Cell. Biol.

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The differentiation of both embryonal carcinoma (EC) and embryonic stem (ES) cells can be triggered in culture by exposure to retinoic acid and results in the transcriptional induction of both the endogenous mouse keratin 18 (mK18) intermediate filament gene and an experimentally introduced human keratin 18 (K18) gene as well as a variety of other markers characteristic of extraembryonic endoderm. The induction of K18 in EC cells is limited, in part, by low levels of ETS and AP-1 transcription factor activities which bind to sites within a complex enhancer element located within the first intron of K18. RNA levels of ETS-2, c-Jun, and JunB increase upon the differentiation of ES cells and correlate with increased expression of K18. Occupancy of the ETS site, detected by in vivo footprinting methods, correlates with K18 induction in ES cells. In somatic cells, the ETS and AP-1 elements mediate induction by a variety of oncogenes associated with the ras signal transduction pathway. In EC cells, in addition to the induction by these limiting transcription factors, relief from negative regulation is mediated by three silencer elements located within the first intron of the K18 gene. These silencer elements function in F9 EC cells but not their differentiated derivatives, and their activity is correlated with proteins in F9 EC nuclei which bind to the silencers and are reduced in the nuclei of differentiated F9 cells. The induction of K18, associated with the differentiation of EC cells to extraembryonic endoderm, is due to a combination of relief from negative regulation and activation by members of the ETS and AP-1 transcription factor families.

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“…As PKB function is also implicated in tumor development, we were interested to know where periplakin would localize in cells that lack vimentin expression and if differential localization, due to presence or absence of vimentin, may influence PKB function. In contrast to many other breast cancer cell lines, the breast epithelial carcinoma cell line MCF-7 expresses little or no vimentin (Stover et al, 1994;van de Klundert et al, 1992) but high levels of periplakin (Fig. 2), and therefore this cell line was used for confocal microscopy using the periplakin antibodies developed.…”

Section: Periplakin Localizes To Different Cellular Compartmentsmentioning

confidence: 99%

Binding of protein kinase B to the plakin family member periplakin

Heuvel

Vries-Smits

Weeren³

et al. 2002

Journal of Cell Science

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Identification of two silencers flanking an AP-1 enhancer in the vimentin promoter

Cited by 31 publications

References 36 publications

Multiple silencer elements are involved in regulating the chicken vimentin gene.

Multiple silencer elements are involved in regulating the chicken vimentin gene.

AP-1, ETS, and transcriptional silencers regulate retinoic acid-dependent induction of keratin 18 in embryonic cells.

Binding of protein kinase B to the plakin family member periplakin

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