Title: The human pseudoxanthoma elasticum gene ABCC6 is transcriptionally regulated by PLAG family transcription factors
Authors: Ratajewski, Marcin ×
Van de Ven, Willem J M
Bartosz, Grzegorz
Pulaski, Lukasz #
Issue Date: Dec-2008
Publisher: Springer-Verlag
Series Title: Human Genetics vol:124 issue:5 pages:451-63
Abstract: Mutations in the ABCC6 gene are known as causative factors of pseudoxanthoma elasticum (PXE), a connective tissue calcification disorder, but the molecular mechanism of pathogenesis or the physiological function of ABCC6 protein is the subject of intense debate. The ABCC6 gene expression is tightly regulated at the transcriptional level and its tissue-specific distribution is consistent with PXE being a metabolic disease caused by failure of ABCC6 function in organs distant from the diseased sites. In an effort to provide clues to its role by elucidating the mechanisms of its regulation, we identified ABCC6 as a target gene for transcriptional induction by PLAG1 and PLAGL1, transcription factors from the PLAG family of cell cycle progression-related DNA-binding proteins. Both these factors are shown to bind to the same single consensus-binding element in the ABCC6 proximal promoter in cell lines of hepatic and renal origin by reporter gene assay, electrophoretic mobility shift assay and chromatin immunoprecipitation. PLAG-mediated ABCC6 transactivation may play an important role in determining the level of tissue-specific expression of this gene. The described mechanism can also find potential application in therapeutic interventions in forms of PXE related to impaired ABCC6 expression.
ISSN: 0340-6717
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science