Cloning and transcriptional analysis of the promoter of the human type 2 desmocollin gene (DSC2)

Marsden, Mark D.; Collins, Jane; Greenwood, Matthew D.; Adams, Michael J.; Fleming, Tom P.; Magee, Anthony I.; Buxton, Roger S.

doi:10.1016/s0378-1119(96)00715-9

Cited by 24 publications

(22 citation statements)

References 37 publications

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“…Expression of desmosomal components and keratins can be regulated by the same transcription factors. For example, Ap2, HoxC13, Lef-1 and Foxn1, which up-regulate or repress keratin expression, have also been implicated as putative or shown regulators of Dsgs, Dscs, armadillo proteins, and the associated desmosomal components periplakin and envoplakin (Byrne et al 1994;Silos et al 1996;Marsden et al 1997;Adams et al 1998;Aho et al 1999;Maatta et al 2000;Potter et al 2001;Bazzi et al 2009). Understanding how transcriptional programs coordinate the expression of cytoarchitectural building blocks during differentiation will help us better understand epidermal development, hair follicle cycling, wound healing, and responses to environmental exposure.…”

Section: Transcriptional Regulation Of Desmosomal Componentsmentioning

confidence: 99%

Desmosomes: Regulators of Cellular Signaling and Adhesion in Epidermal Health and Disease

Johnson

Najor

Green

2014

Cold Spring Harbor Perspectives in Medicine

119

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Section: Transcriptional Regulation Of Desmosomal Componentsmentioning

confidence: 99%

Desmosomes: Regulators of Cellular Signaling and Adhesion in Epidermal Health and Disease

Johnson

Najor

Green

2014

Cold Spring Harbor Perspectives in Medicine

119

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“…Although other cell-cell adhesion proteins are recognized as Cdx transcriptional targets (11,12), this would be the first report to tie Cdx1 and Cdx2 to the regulation of intestinal cell desmosomes and DSC2 gene expression. Moreover, it is the first report to our knowledge exploring the molecular regulation of the DSC2 promoter and DSC2 gene expression since a description of the gene was first published (4,25).…”

Section: Mol Cancer Res 2008;6(9) September 2008mentioning

confidence: 99%

“…The desmocollin cadherins are membrane-spanning glycoproteins that function as Ca 2+ -dependent cell adhesion molecules (1,3). DSC2 has the widest tissue distribution in epithelia and desmosome-bearing nonepithelial tissues (4). DSC1 and DSC3 are restricted to stratified epithelia and cardiac muscle (5).…”

Section: Introductionmentioning

confidence: 99%

Repression of the Desmocollin 2 Gene Expression in Human Colon Cancer Cells Is Relieved by the Homeodomain Transcription Factors Cdx1 and Cdx2

Funakoshi

Ezaki

Kong

et al. 2008

Molecular Cancer Research

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Desmosomes are intracellular junctions that provide strong cell-cell adhesion in epithelia and cardiac muscle. Their disruption causes several human diseases and contributes to the epithelial-to-mesenchymal transition observed in cancer. Desmocollin 2 (DSC2) is a cadherin superfamily member and a critical component of desmosomes found in intestinal epithelium. However, the mechanism regulating DSC2 gene expression in intestinal cells is not known. Cdx1 and Cdx2 are homeodomain transcription factors that regulate intestine-specific gene expression. Cdx expression in the past has been associated with the induction of desmosomes. We now show that the DSC2 gene is a transcriptional target for Cdx1 and Cdx2. Colon cancer cell lines retaining Cdx2 expression typically express DSC2. Restoration of Cdx expression in Colo 205 cells induced DSC2 mRNA and protein and the formation of desmosomes. The 5 ¶-flanking region of the DSC2 promoter contains two consensus Cdx-binding sites. Electrophoretic mobility shift assays show that Cdx1 and Cdx2 bind these sites in vitro, and chromatin immunoprecipitation confirmed Cdx2 binding in vivo. DSC2 promoter truncations established that these regions are Cdx responsive. The truncations also identify a region of the promoter in which potent transcriptional repressors act. This repressor activity is relieved by Cdx binding. We conclude that the homeodomain transcription factors Cdx1 and Cdx2 regulate DSC2 gene expression in intestinal epithelia by reversing the actions of a transcriptional repressor. The regulation of desmosomal junctions by Cdx contributes to normal intestinal epithelial columnar morphology and likely antagonizes the epithelial-to-mesenchymal transition necessary for the metastasis of colon cancer cells in humans.

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“…Desmocollin 2 (Dsc2), a component of desmosomes, is expressed primarily in epithelial cells, serves an integral role in cell adhesion by forming links with the intermediate filament network (Marsden et al, 1997), and was inhibited by TCDD. TCDD also inhibited Perp induction, which promotes desmosomal complex assembly (Ihrie et al, 2005).…”

Section: Estrogen-tcdd Uterine Gene Expression Cross-talk 89mentioning

confidence: 99%

Inhibition of Estrogen-Mediated Uterine Gene Expression Responses by Dioxin

Boverhof

Burgoon

Williams³

et al. 2007

Mol Pharmacol

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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exhibits antiestrogenic properties, including the inhibition of estrogen-induced uterine growth and proliferation. The inhibition of estrogenmediated gene expression through ER/AhR cross-talk has been proposed as a plausible mechanism; however, only a limited number of inhibited responses have been investigated that are unlikely to fully account for the antiuterotrophic effects of TCDD. Therefore, the effects of TCDD on ethynyl estradiol (EE)-mediated uterine gene expression were investigated using cDNA microarrays with complementary physiological and histological phenotypic anchoring. Mice were gavaged with vehicle, 3 daily doses of 10 g/kg EE, a single dose of 30 g/kg TCDD, or a combination of EE plus TCDD and sacrificed after 4, 12, 24, and 72 h. TCDD cotreatment inhibited EE-induced uterine wet weight by 37, 23, and 45% at 12, 24, and 72 h, respectively. TCDD cotreatment also reduced EE-mediated stromal edema, hypertrophy, and hyperplasia and induced marked luminal epithelial cell apoptosis. A 2 ϫ 2 factorial microarray design was used to identify EE-and TCDD-specific differential gene expression responses as well as their interactive effects. Only 133 of the 2753 EE-mediated differentially expressed genes were significantly modulated by TCDD cotreatment, indicating a gene-specific inhibitory response. The EE-mediated induction of many genes, including trefoil factor 1 and keratin 14, were inhibited by greater than 90% by TCDD. Functional annotation of inhibited responses was associated with cell proliferation, water and ion transport, and maintenance of cellular structure and integrity. These inhibited responses correlate with the observed histological alterations and may contribute to the antiuterotrophic effects of TCDD.Estrogens regulate growth, development, and reproductive function in men and women and have been implicated in the etiology of breast and endometrial cancers (Hewitt et al., 2005). Many estrogen effects are mediated through the estrogen receptor (ER), a ligand-activated transcription factor and member of the nuclear receptor superfamily (Nilsson et al., 2001). In the traditional mechanism, ligand binding to the ER results in dissociation from heat shock and chaperone proteins, homodimerization, and interaction with regulatory elements near estrogen-responsive genes known as estrogen response elements (EREs) (Klinge, 2001). However, the activated ER can also mediate effects via interactions with Fos/ Jun at AP-1 sites, via Sp1 at GC-rich promoter regions (Hall et al., 2001;Nilsson et al., 2001), and through ligand-independent, DNA binding-independent, and cell-surface (nongenomic) signaling mechanisms (Hall et al., 2001). These ER-mediated alterations in gene expression and signaling pathways are responsible for the subsequent molecular and physiological responses to estrogens.Like the ER, the aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor but is a member of the basic helix-loop-helix-PER/ARNT/SIM (periodicity/a...

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Cloning and transcriptional analysis of the promoter of the human type 2 desmocollin gene (DSC2)

Cited by 24 publications

References 37 publications

Desmosomes: Regulators of Cellular Signaling and Adhesion in Epidermal Health and Disease

Desmosomes: Regulators of Cellular Signaling and Adhesion in Epidermal Health and Disease

Repression of the Desmocollin 2 Gene Expression in Human Colon Cancer Cells Is Relieved by the Homeodomain Transcription Factors Cdx1 and Cdx2

Inhibition of Estrogen-Mediated Uterine Gene Expression Responses by Dioxin

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