Structure and nucleotide sequence of the 5' region of the human and feline c-sis proto-oncogenes

Ouweland, Ans M.W. van den; Roebroek, Anton; Schalken, Jack A.; Claesen, C. A. A.; Bloemers, H. P. J.; Ven, Wim J.M. Van de

doi:10.1093/nar/14.2.765

Cited by 24 publications

(21 citation statements)

References 41 publications

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“…Another possible cause of inaccessibility of the c-sis promoter for activating transcription factors is methylation of essential CpG dinucleotides. Four CpG dinucleotides are located within the first 100 bp upstream of the c-sis transcriptioninitiation site (van den Ouweland et al, 1986) and their methylation status is currently being examined.…”

Section: Discussionmentioning

confidence: 99%

“…A site at + 0.4, which extends from approximate position + 280 to + 500, was found in the c-sis expressing carcinoma-derived cell lines, but is absent from the placenta cell lines and from K562 cells. Although this site could not be linked to a clear function with respect to transcription regulation, it contains a CpG island (van den Ouweland et al, 1986) and may bind trans-acting factors in vivo (Fig. 4).…”

Section: Discussionmentioning

confidence: 99%

“…pA068, pA0121, pA0125 and pA0152 are subclones of genomic c-sis clone ALLW-1283-C1 21 (van den Ouweland et a]., 1985). pA068 and pAOl21 have been described earlier (van den Ouweland et al, 1985(van den Ouweland et al, , 1986. pA0125 consists of a 14-kb HindIII-EcoRI fragment cloned in pAT153; pA0152 consists of a 1.9-kb HindIII-BamHI fragment cloned in pAT153.…”

Section: Dna Probesmentioning

confidence: 99%

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Localization and functional analysis of DNase‐I‐hypersensitive sites in the human c‐sis/PDGF‐B gene transcription unit and its flanking regions

Dirks

Jansen

Gerritsma

et al. 1993

European Journal of Biochemistry

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We studied the regulation of the expression of the human c-sisfPDGF-B gene in the following panel of cell lines : K562 cells, in which expression is inducible by phorbol esters ; cytotrophoblastderived cell lines JEG-3 and JAR; carcinoma-derived cell lines PC3, T24 and HeLa, which show extensive differences in c-sis mRNA content; dermal fibroblasts, which do not express the gene. We demonstrate that the wide variety of levels of c-sis mRNA in these cells is mainly determined at the transcription level. Extensive gene rearrangements or amplifications, or significant differences in the stability of the c-sis transcript could not be found. In fibroblasts and placenta cell lines, inaccessibility of the c-sis promoter, rather than the absence of transcription factors that activate it, inhibits expression of the endogenous gene. Examination of the chromatin structure of the transcription unit and immediate flanking regions revealed several cell-type-specific DNase-I-hypersensitivity (DH) sites. Functional analysis of genomic fragments harbouring one or more DH sites showed the presence of negative regulatory elements within intron 1, and of an activating element downstream of the gene. A DH site, located immediately downstream of the promoter in dermal fibroblasts, may regulate accessibility of the promoter by means of specific nucleosome phasing.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Dna Probesmentioning

confidence: 99%

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Localization and functional analysis of DNase‐I‐hypersensitive sites in the human c‐sis/PDGF‐B gene transcription unit and its flanking regions

Dirks

Jansen

Gerritsma

et al. 1993

European Journal of Biochemistry

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“…Using deletion mutagenesis and the cat reporter gene, we identified a minimum region of 42 bp upstream of the TATA box which was required for promoter activity in uninduced cells (Fig. 7).…”

Section: Discussionmentioning

confidence: 99%

Functional identification of regulatory elements within the promoter region of platelet-derived growth factor 2.

et al. 1989

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Human platelet-derived growth factor (PDGF) is composed of two polypeptide chains, PDGF-1 and PDGF-2, the human homolog of the v-sis oncogene. Deregulation of PDGF-2 expression can confer a growth advantage to cells possessing the cognate receptor and, thus, may contribute to the malignant phenotype. We investigated the regulation of PDGF-2 mRNA expression during megakaryocytic differentiation of K562 cells. Induction by 12-O-tetradecanoylphorbol-13-acetate (TPA) led to a greater than 200-fold increase in PDGF-2 transcript levels in these cells. Induction was dependent on protein synthesis and was not enhanced by cycloheximide exposure. In our initial investigation of the PDGF-2 promoter, a minimal promoter region, which included sequences extending only 42 base pairs upstream of the TATA signal, was found to be as efficient as 4 kilobase pairs upstream of the TATA signal in driving expression of a reporter gene in uninduced K562 cells. We also functionally identified different regulatory sequence elements of the PDGF-2 promoter in TPA-induced K562 cells. One region acted as a transcriptional silencer, while another region was necessary for maximal activity of the promoter in megakaryoblasts. This region was shown to bind nuclear factors and was the target for trans-activation in normal and tumor cells. In one tumor cell line, which expressed high PDGF-2 mRNA levels, the presence of the positive regulatory region resulted in a 30-fold increase in promoter activity. However, the ability of the minimal PDGF-2 promoter to drive reporter gene expression in uninduced K562 cells and normal fibroblasts, which contained no detectable PDGF-2 transcripts, implies the existence of other negative control mechanisms beyond the regulation of promoter activity.

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“…Sp1 has been shown to contain several independent transcriptional activation domains in addition to the zinc finger region located within the C terminus of the protein (46) We have demonstrated that the ThR segment within the B region of the PDGF B-chain gene is involved in the transcriptional response to thrombin. The conservation of the ThR region of the PDGF B-chain gene across different species (human (52), feline (52), and murine (53)) suggests that the region may serve as a binding site for important cis-acting elements. If this region is in fact a site responsive to a thrombin-induced transcriptional activator, then one might anticipate finding the CCACCC motif within the promoter region of other thrombinresponsive genes.…”

Section: Interaction Of Sp1 and Tinf With The B Region Of The Pdgf B-mentioning

confidence: 99%

Identification of a Thrombin Response Element in the Human Platelet-derived Growth Factor B-chain (c-sis) Promoter

Scarpati

DiCorleto

1996

Journal of Biological Chemistry

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Thrombin is a coagulation system protease that also serves as a potent stimulator of gene expression in several cell types, including endothelial cells (EC). We and others have previously demonstrated that the transcription of platelet-derived growth factor (PDGF) B-chain (c-sis) by EC is stimulated severalfold by thrombin. Here we examine the molecular mechanism of this regulatory process using bovine aortic EC transiently transfected with a vector containing the chloramphenicol acetyltransferase (CAT) gene under the control of a 400-base pair fragment of the human PDGF B-chain promoter. Thrombin treatment of these cells caused a severalfold increase in CAT expression. Deletion analysis and sitedirected mutagenesis revealed that the region spanning nucleotides ؊61 to ؊53 from the transcription initiation site (referred to as the thrombin response, or ThR, region) was critical for the transcriptional response to thrombin. Electrophoretic mobility shift assays with an oligonucleotide corresponding to the region ؊64 to ؊44, which contained the ThR region, led to the identification of a thrombin-inducible nuclear factor (TINF) in extracts from thrombin-treated, but not control, EC. TINF was formed as early as 40 min post-thrombin treatment, persisted for at least 7 h, but was no longer present after 24 h. TINF appeared in the absence of de novo protein synthesis. The ThR region consists of a repeat of a CCACCC element in an ABBA configuration, which, based on mutation analysis and transfection assays, appears to be critical in mediating thrombin stimulation of the PDGF B-chain gene. The conservation of the ThR region in the promoter of the PDGF B-chain among three species (human, feline, and murine) further supports the importance of this region as a cis-acting regulatory element.

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Structure and nucleotide sequence of the 5' region of the human and feline c-sis proto-oncogenes

Cited by 24 publications

References 41 publications

Localization and functional analysis of DNase‐I‐hypersensitive sites in the human c‐sis/PDGF‐B gene transcription unit and its flanking regions

Localization and functional analysis of DNase‐I‐hypersensitive sites in the human c‐sis/PDGF‐B gene transcription unit and its flanking regions

Functional identification of regulatory elements within the promoter region of platelet-derived growth factor 2.

Identification of a Thrombin Response Element in the Human Platelet-derived Growth Factor B-chain (c-sis) Promoter

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