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Transcription profiling of mouse dermal fibroblasts following exposure to endothelin-1


ABSTRACT: To determine if aberrant activation of endothelin-1 (Et1) could lead to the dysregulation of many downstream genes, we exposed fibroblasts to exogenous ET1 peptide and assayed for transcriptional changes by microarray. Mouse dermal fibroblasts were treated with exogenous Et1 peptide for 24 hours. ET1 treatment resulted in significant expression changes - primarily downregulation - of a number of genes. In particular, Tgf-beta-2 and Tgf-beta-3 were among the downregulated genes, which in turn alter the expression status of their many target genes. These data suggest that the stable silencing of Et1 is important for the phenotypic stability of dermal fibroblasts, and perhaps many other cell types as well.

Three separate biological replicates were derived for both control and treated samples. The primary dermal fibroblasts were derived by explant procedure from the skin of mouse pups aged 0-3 days. By passage 5, cells were split to two separate cultures-- one with 100nM synthetic Et1 peptide added to the medium (treated) and the other with nothing added (control). Cells were exposed to Et1 for 24 hrs, then treated and control populations were harvested for total RNA.

ORGANISM(S): Mus musculus

SUBMITTER: Tammy Vallender 

PROVIDER: E-GEOD-4695 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Localized methylation in the key regulator gene endothelin-1 is associated with cell type-specific transcriptional silencing.

Vallender Tammy W TW   Lahn Bruce T BT  

FEBS letters 20060714 18


DNA methylation can contribute to the stable transcriptional silencing of mammalian genes. Often times, these genes are important developmental regulators, and their silencing in cell types where they are not supposed to be active is important for the phenotypic stability of the cells. To identify key developmental regulator genes whose expression in terminally differentiated cells may be inhibited by DNA methylation, mouse dermal fibroblasts were demethylated with 5-aza-2'-deoxycytidine, and ch  ...[more]

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