A role for insulator elements in the regulation of gene expression response to hypoxia
Entity
UAM. Departamento de BioquímicaPublisher
Oxford University PressDate
2012-03-01Citation
10.1093/nar/gkr842
Nucleic Acids Research 40.5 (2012): 1916-1927
ISSN
0305-1048 (print); 1362-4962 (online)DOI
10.1093/nar/gkr842Funded by
The Ministerio de Ciencia e Innovación (Spanish Ministry of Science and Innovation, MICINN) grant numbers Nucleic Acids Research, 2012, Vol. 40, No. 5 1925 SAF2008-03147 (to L.del P.), BIO2009-1297 (to L.M.), BFU2010-14839 (to J.L.G.-S.), CSD2007-00008 (to J.L.G.-S.); Comunidad Autónoma de Madrid grant number S-SAL-0311_2006 (to L.del P.); the 7th Research Framework Programme of the European Union grant number METOXIA project ref. HEALTH-F2-2009-222741 (to L.del P.); Junta de Andalucía grant number CVI-3488 (to J.L.G.-S.); CIBERER (ISCIII) (to E.M.). Funding for open access charge: SAF2008-03147 (to L.del P.)Project
Comunidad de Madrid. S2006/SAL-0311; info:eu-repo/grantAgreement/EC/FP7/222741Subjects
Carrier Proteins; DNA; Gene Expression Regulation; Glycogen Synthase; Insulator Elements; MedicinaRights
© 2011 The Author(s)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 (∼1kb) 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
Files in this item
Google Scholar:Tiana, María
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Villar Lozano, Diego
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Pérez-Guijarro, Eva
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Gómez-Maldonado, Laura
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Moltó, Eduardo
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Fernández-Miñán, Ana
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Gómez-Skármeta, José Luis
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Montoliu, Lluís
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Del Peso, Luis
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