Novel salivary gland specific binding elements located in the PSP proximal enhancer core

Svendsen, Pia; Laursen, Jesper; Krogh-Pedersen, Helene; Hjorth, J.

doi:10.1093/nar/26.11.2761

Cited by 8 publications

(26 citation statements)

References 23 publications

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“…Expression Vector and Luciferase Reporter Gene Constructs-An 885-bp PSP promoter fragment from Ϫ889 to Ϫ4 of the PSP gene (34) was cloned from murine genomic DNA by PCR and cloned into the pCRII TA cloning vector. The EcoRI-linked PSP promoter was transferred into the EcoRI site of the pGL3 luciferase vector.…”

Section: Sequence 19mentioning

confidence: 99%

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Characterization of ESE-2, a Novel ESE-1-related Ets Transcription Factor That Is Restricted to Glandular Epithelium and Differentiated Keratinocytes

Oettgen¹,

Kas²,

Dube³

et al. 1999

Journal of Biological Chemistry

118

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Epithelial cell differentiation is tightly controlled by distinct sets of transcription factors that regulate the expression of stage-specific genes. We recently isolated the first epithelium-specific Ets transcription factor (ESE-1). Here we describe the characterization of ESE-2, a second epithelium-restricted ESE-1-related Ets factor. Like ESE-1, ESE-2 is induced during keratinocyte differentiation. However, whereas ESE-1 is expressed in the majority of epithelial cell types, ESE-2 expression is restricted to differentiated keratinocytes and glandular epithelium such as salivary gland, prostate, mammary gland, and kidney. In contrast to ESE-1, full-length ESE-2 binds poorly to DNA due to the presence of a negative regulatory domain at the amino terminus. Furthermore, although ESE-1 and the amino-terminally deleted ESE-2 bind with similar affinity to the canonical E74 Ets site, ESE-2 and ESE-1 differ strikingly in their relative affinity toward binding sites in the c-MET and PSMA promoters. Similarly, ESE-1 and ESE-2 drastically differ in their ability to transactivate epitheliumspecific promoters. Thus, ESE-2, but not ESE-1, transactivates the parotid gland-specific PSP promoter and the prostate-specific PSA promoter. In contrast, ESE-1 transactivates the keratinocyte-specific SPRR2A promoter Ets site and the prostate-specific PSMA promoter significantly better than ESE-2. Our results demonstrate the existence of a unique class of related epitheliumspecific Ets factors with distinct functions in epithelial cell gene regulation.Normal epithelial cell development, proliferation, and differentiation are induced by mesenchymal-epithelial interactions and involve cell-cell interactions, extracellular matrix, and soluble growth and differentiation factors. These interactions trigger the activation or expression of a distinct set of transcription factors leading to a specific pattern of gene expression along a tightly controlled pathway. Abnormalities in this process due to deregulated gene expression can lead to the development of benign adenomas or malignant carcinomas that make up the majority of solid tumors. In order to understand tumor development, it is therefore critical to understand normal epithelial cell differentiation and proliferation. Whereas rapid progress in understanding immune system development and gene regulation has led to the discovery and characterization of a whole set of genes involved in leukemia and lymphoma development, relatively little is known about epithelial cell differentiation and organ development and the mechanisms involved in solid tumor formation. Most of the genes involved in chromosomal translocations in leukemias and lymphomas encode transcription factors that under normal physiological conditions coordinate the correct spatial and temporal expression of genes (1). We therefore postulate that similar mechanisms of oncogenesis play a role in epithelium-derived tumors as well. It is thus surprising that many aspects of epithelium-specific gene expression have not been explore...

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Section: Sequence 19mentioning

confidence: 99%

“…The PSP gene contains a promoter and enhancer region that both are critical regulatory components for parotid gland-specific expression (34). However, the cell type-specific regulatory elements have not been characterized.…”

Section: Fig 7 Expression Of Ese-2 Ese-1 and Elf-1 During Keratinmentioning

confidence: 99%

Characterization of ESE-2, a Novel ESE-1-related Ets Transcription Factor That Is Restricted to Glandular Epithelium and Differentiated Keratinocytes

Oettgen¹,

Kas²,

Dube³

et al. 1999

Journal of Biological Chemistry

118

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“…Three Lama-∆Bsm transgenes, ∆Bsm-∆PGE I, ∆Bsm-∆PGE II and ∆Bsm-∆PGE IjII, deleted specifically for PGE I, PGE II or both respectively, were constructed using the transformer site-directed mutagenesis kit (Clontech Laboratories, Inc.), as described by the manufacturer. A pUC19 plasmid containing the proximal PSP enhancer region (k4.6 HindIII to k3.1 StuI) [7] inserted between HindIII and HincII was used as the target plasmid [8]. The selection primer changed the NdeI restriction site in pUC19 into a unique NcoI site.…”

Section: Experimental Transgene Construction and Generation Of Transgmentioning

confidence: 99%

“…Transgenic mRNA was detected with an oligonucleotide specific for the Lama construct [4]. mRNA expression levels were estimated as described previously [6,7] using a cDNA probe recognizing the transgene as well as the endogenous PSP mRNA [4].…”

Section: Northern Blot Analysismentioning

confidence: 99%

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Protein-binding elements in the proximal parotid secretory protein gene enhancer essential for salivary-gland-specific expression

Svendsen

Kristiansen

Hjorth

2001

Biochemical Journal

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The murine parotid secretory protein (PSP) gene is expressed at high levels in the parotid gland and at lower levels in the sublingual gland. A proximal enhancer core necessary for tissue-specific expression was identified previously, and it was demonstrated that one element, parotid gland element I (PGE I), exhibited specific binding of parotid gland nuclear proteins. In the present study, we demonstrate that a related adjacent element, PGE II, which binds nuclear proteins in a much less tissue-restricted manner, is able to compete with PGE I for binding of parotid-gland-specific factors. The functional significance of PGE I and PGE II was examined in transgenic mice. Deletion of PGE II reduced transgene expression only in the parotid gland, whereas deletion of PGE I appeared to reduce expression in both of the PSP-expressing salivary glands. Combined deletion of PGE I and PGE II reduced expression below the limit of detection. Thus PGE I and PGE II are functionally important salivary-gland-specific binding elements that are necessary for the salivary-gland-specific expression of a PSP minigene in transgenic mice.

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Analysis of cDNA sequence, protein structure and expression of parotid secretory protein in pig

et al. 2003

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Novel salivary gland specific binding elements located in the PSP proximal enhancer core

Cited by 8 publications

References 23 publications

Characterization of ESE-2, a Novel ESE-1-related Ets Transcription Factor That Is Restricted to Glandular Epithelium and Differentiated Keratinocytes

Characterization of ESE-2, a Novel ESE-1-related Ets Transcription Factor That Is Restricted to Glandular Epithelium and Differentiated Keratinocytes

Protein-binding elements in the proximal parotid secretory protein gene enhancer essential for salivary-gland-specific expression

Analysis of cDNA sequence, protein structure and expression of parotid secretory protein in pig

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