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首页> 外文期刊>Biochimica et Biophysica Acta. Gene Regulatory Mechanisms >Hypoxia controls Flvcr1 gene expression in Caco2 cells through HIF2α and ETS1
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Hypoxia controls Flvcr1 gene expression in Caco2 cells through HIF2α and ETS1

机译：缺氧通过HIF2α和ETS1控制Caco2细胞中Flvcr1基因的表达

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The tissue-specific gene expression changes mediated by the hypoxia inducible factors (HIFs) allow the adaptation of cells to low oxygen tension and control several processes including erythropoiesis, angiogenesis and vasculogenesis. The Feline Leukemia Virus, subgroup C, Receptor 1 (Flvcr1) gene encodes for two isoforms, Flvcr1a and 1b, involved in the export of heme out of the cell and of mitochondria respectively. Studies in mouse models demonstrated a crucial role of Flvcr1 isoforms in erythropoiesis and during embryo development.Here, we showed the modulation of Flvcr1 gene expression in different tissues and cell lines in response to hypoxia. Chromatin immunoprecipitation analysis demonstrated that HIF2α and HIF-dependent transcription factor ETS1 (v-ets avian erythroblastosis virus E26 oncogene homolog 1) bind at the region - 318/+. 39 of the Flvcr1 promoter. Analysis of Caco2 cells in which HIF2α or ETS1 were silenced or overexpressed demonstrated that, both HIF2α and ETS1 are involved in the transcriptional regulation of Flvcr1a and that HIF2α is absolutely required for Flvcr1a induction upon hypoxia.The inclusion of the Flvcr1 gene in the group of HIF2α-responsive genes strengthens its role in hypoxia-stimulated processes like erythropoiesis, vasculogenesis and heme absorption.
机译：由缺氧诱导因子（HIFs）介导的组织特异性基因表达变化使细胞适应低氧张力并控制包括红细胞生成，血管生成和血管生成在内的多个过程。猫白血病病毒C亚型受体1（Flvcr1）基因编码两个同工型Flvcr1a和1b，分别参与血红素从细胞和线粒体的输出。在小鼠模型中的研究表明Flvcr1亚型在红细胞生成和胚胎发育过程中起着至关重要的作用。在这里，我们展示了Flvcr1基因在不同组织和细胞系中对缺氧反应的调控。染色质免疫沉淀分析表明，HIF2α和HIF依赖性转录因子ETS1（v-ets禽成红细胞病病毒E26癌基因同源物1）在318 / +区域结合。 Flvcr1启动子的39。分析HIF2α或ETS1沉默或过表达的Caco2细胞表明，HIF2α和ETS1均参与Flvcr1a的转录调控，缺氧时诱导Flvcr1a绝对需要HIF2α。 HIF2α反应基因在缺氧刺激的过程（如红细胞生成，血管生成和血红素吸收）中增强其作用。

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