ArticleNucleic acids research2012
A role for insulator elements in the regulation of gene expression response to hypoxia.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 18 citations in OpenAlex.
- Beyond gluten: the multifaceted regulation of MHC class II in celiac disease pathogenesis.Gastroenterology and hepatology from bed to bench · 2025Review
- Article
- Identification of non-coding genetic variants in samples from hypoxemic respiratory disease patients that affect the transcriptional response to hypoxia.Nucleic acids research · 2016Article
- MIR retrotransposon sequences provide insulators to the human genome.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Functional validation of mouse tyrosinase non-coding regulatory DNA elements by CRISPR-Cas9-mediated mutagenesis.Nucleic acids research · 2015Article
- Article
- Transient estrogen receptor binding and p300 redistribution support a squelching mechanism for estradiol-repressed genes.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Transcriptional directionality of the human insulin-degrading enzyme promoter.Molecular and cellular biochemistry · 2013Article
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia inducible factor (HIF) up-regulates the transcription of a few hundred genes required for the adaptation to hypoxia. This restricted set of targets is in sharp contrast with the widespread distribution of the HIF binding motif throughout the genome. Here, we investigated the transcriptional response of GYS1 and RUVBL2 genes to hypoxia to understand the mechanisms that restrict HIF activity toward specific genes. GYS1 and RUVBL2 genes are encoded by opposite DNA strands and separated by a short intergenic region (~1 kb) that contains a functional hypoxia response element equidistant to both genes. However, hypoxia induced the expression of GYS1 gene only. Analysis of the transcriptional response of chimeric constructs derived from the intergenic region revealed an inhibitory sequence whose deletion allowed RUVBL2 induction by HIF. Enhancer blocking assays, performed in cell culture and transgenic zebrafish, confirmed the existence of an insulator element within this inhibitory region that could explain the differential regulation of GYS1 and RUVBL2 by hypoxia. Hence, in this model, the selective response to HIF is achieved with the aid of insulator elements. This is the first report suggesting a role for insulators in the regulation of differential gene expression in response to environmental signals.
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