ABCC6 Expression is Regulated by CCAAT/enhancer-binding Protein Activating a Primate-specific Sequence Located in the First Intron of the Gene

Overview

Journal J Invest Dermatol

Publisher Elsevier

Specialty Dermatology

Date 2012 Jul 6

PMID 22763786

Citations 13

Authors

Marcin Ratajewski

Hugues de Boussac

Iwona Sachrajda

Caroline Bacquet

Tunde Kovacs

Andras Varadi

Lukasz Pulaski

Tamas Aranyi

Affiliations

Soon will be listed here.

Abstract

Pseudoxanthoma elasticum (PXE), a rare recessive genetic disease causing skin, eye, and cardiovascular lesions, is characterized by the calcification of elastic fibers. The disorder is due to loss-of-function mutations of the ABCC6 gene, but the pathophysiology of the disease is still not understood. Here we investigated the transcriptional regulation of the gene, using DNase I hypersensitivity assay followed by luciferase reporter gene assay. We identified three DNase I hypersensitive sites (HSs) specific to cell lines expressing ABCC6. These HSs are located in the proximal promoter and in the first intron of the gene. We further characterized the role of the HSs by luciferase assay and demonstrated the transcriptional activity of the intronic HS. We identified the CCAAT/enhancer-binding protein β (C/EBPβ) as a factor binding the second intronic HS by chromatin immunoprecipitation and corroborated this finding by luciferase assays. We also showed that C/EBPβ interacts with the proximal promoter of the gene. We propose that C/EBPβ forms a complex with other regulatory proteins including the previously identified regulatory factor hepatocyte nuclear factor 4α (HNF4α). This complex would account for the tissue-specific expression of the gene and might serve as a metabolic sensor. Our results point toward a better understanding of the physiological role of ABCC6.

Citing Articles

Epigenetic regulation of the human gene.

Karas K, Pastwinska J, Salkowska A, Karwaciak I, Ratajewski M Biochem Biophys Rep. 2024; 40:101827.

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Bone Marrow-Derived ABCC6 Is an Essential Regulator of Ectopic Calcification In Pseudoxanthoma Elasticum.

Brampton C, Pomozi V, Le Corre Y, Zoll J, Kauffenstein G, Ma C J Invest Dermatol. 2024; 144(8):1772-1783.e3.

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The Expression Level of ABCC6 Transporter in Colon Cancer Cells Correlates with the Activation of Different Intracellular Signaling Pathways.

Abruzzese V, Sukowati C, Tiribelli C, Matera I, Ostuni A, Bisaccia F Pathophysiology. 2022; 29(2):173-186.

PMID: 35645325 PMC: 9149812. DOI: 10.3390/pathophysiology29020015.

Sex-specific regulation of aging in Caenorhabditis elegans.

Hotzi B, Kosztelnik M, Hargitai B, Takacs-Vellai K, Barna J, Borden K Aging Cell. 2018; 17(3):e12724.

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The ABCC6 Transporter: A New Player in Biomineralization.

Favre G, Laurain A, Aranyi T, Szeri F, Fulop K, Le Saux O Int J Mol Sci. 2017; 18(9).

PMID: 28891970 PMC: 5618590. DOI: 10.3390/ijms18091941.

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