Tausendschoen, Michaela and Rehli, Michael and Dehne, Nathalie and Schmidl, Christian and Doring, Claudia and Hansmann, Martin-Leo and Bruene, Bernhard (2015) Genome-wide identification of hypoxia-inducible factor-1 and -2 binding sites in hypoxic human macrophages alternatively activated by IL-10. BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, 1849 (1). pp. 10-22. ISSN 1874-9399, 0006-3002
Full text not available from this repository. (Request a copy)Abstract
Macrophages (M Phi) often accumulate in hypoxic areas, where they significantly influence disease progression. Anti-inflammatory cytokines, such as IL-10, generate alternatively activated macrophages that support tumor growth. To understand how alternative activation affects the transcriptional profile of hypoxic macrophages, we globally mapped binding sites of hypoxia-inducible factor (HIF)-1 alpha and HIF-2 alpha in primary human monocyte-derived macrophages prestimulated with IL-10. 713 HIF-1 and 795 HIF-2 binding sites were identified under hypoxia. Pretreatment with IL-10 altered the binding pattern, with 120 new HIF-1 and 188 new HIF-2 binding sites emerging. HIF-1 binding was most prominent in promoters, while HIF-2 binding was more abundant in enhancer regions. Comparison of ChIP-seq data obtained in other cells revealed a highly cell type specific binding of HIF. In M Phi HIF binding occurred preferentially in already active enhancers or promoters. To assess the roles of HIF on gene expression, primary human macrophages were treated with siRNA against HIF-1 alpha or HIF-2 alpha, followed by genome-wide gene expression analysis. Comparing mRNA expression to the HIF binding profile revealed a significant enrichment of hypoxia-inducible genes previously identified by ChIP-seq. Analysis of gene expression under hypoxia alone and hypoxia/IL-10 showed the enhanced induction of a set of genes including PLOD2 and SLC2A3, while another group including KDM3A and ADM remained unaffected or was reduced by IL-10. Taken together IL-10 influences the DNA binding pattern of HIF and the level of gene induction (C) 2014 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSCRIPTION FACTORS; GENE-EXPRESSION; COOPERATIVE INTERACTION; FACTORS HIF-1-ALPHA; SIGNALING PATHWAYS; HUMAN MONOCYTES; FACTOR 1-ALPHA; HIF-BINDING; KAPPA-B; CELLS; Hypoxia; ChIP-seq; Enhancer; Promoter |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Aug 2019 10:50 |
| Last Modified: | 02 Aug 2019 10:50 |
| URI: | https://pred.uni-regensburg.de/id/eprint/6327 |
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