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Open AccessArticle

The Expression of Decidual Protein Induced by Progesterone (DEPP) Is Controlled by Three Distal Consensus Hypoxia Responsive Element (HRE) in Hypoxic Retinal Epithelial Cells

1
Department of Ophthalmology, Lab for Retinal Cell Biology, University of Zurich, 8952 Schlieren, Switzerland
2
Center for Integrative Human Physiology (ZIHP), University of Zurich, 8006 Zurich, Switzerland
3
Institute of Medical Molecular Genetic, University of Zurich, 8952 Schlieren, Switzerland
4
Neuroscience Center, University of Zurich, 8006 Zurich, Switzerland
*
Author to whom correspondence should be addressed.
Genes 2020, 11(1), 111; https://doi.org/10.3390/genes11010111
Received: 19 November 2019 / Revised: 10 January 2020 / Accepted: 14 January 2020 / Published: 18 January 2020
(This article belongs to the Special Issue Molecular Genetics of Retinal Dystrophies)
Hypoxia affects the development and/or progression of several retinopathies. Decidual protein induced by progesterone (DEPP) has been identified as a hypoxia-responsive gene that may be part of cellular pathways such as autophagy and connected to retinal diseases. To increase our understanding of DEPP regulation in the eye, we defined its expression pattern in mouse and human retina and retinal pigment epithelium (RPE). Interestingly, DEPP expression was increased in an age-dependent way in the central human RPE. We showed that DEPP was regulated by hypoxia in the mouse retina and eyecup and that this regulation was controlled by hypoxia-inducible transcription factors 1 and 2 (HIF1 and HIF2). Furthermore, we identified three hypoxia response elements (HREs) about 3.5 kb proximal to the transcriptional start site that were responsible for hypoxic induction of DEPP in a human RPE cell line. Comparative genomics analysis suggested that one of the three HREs resides in a highly conserved genomic region. Collectively, we defined the molecular elements controlling hypoxic induction of DEPP in an RPE cell line, and provided evidence for an enrichment of DEPP in the aged RPE of human donors. This makes DEPP an interesting gene to study with respect to aging and age-related retinal pathologies. View Full-Text
Keywords: decidual protein induced by progesterone (DEPP); hypoxia; retinal pigment epithelium (RPE); retina; hypoxia responsive element (HRE) decidual protein induced by progesterone (DEPP); hypoxia; retinal pigment epithelium (RPE); retina; hypoxia responsive element (HRE)
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Klee, K.; Storti, F.; Maggi, J.; Todorova, V.; Karademir, D.; Berger, W.; Samardzija, M.; Grimm, C. The Expression of Decidual Protein Induced by Progesterone (DEPP) Is Controlled by Three Distal Consensus Hypoxia Responsive Element (HRE) in Hypoxic Retinal Epithelial Cells. Genes 2020, 11, 111.

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