PUBLICATION

A role for insulator elements in the regulation of gene expression response to hypoxia

Authors
Tiana, M., Villar, D., Pérez-Guijarro, E., Gómez-Maldonado, L., Moltó, E., Fernández-Miñán, A., Gómez-Skarmeta, J.L., Montoliu, L., and Del Peso, L.
ID
ZDB-PUB-111117-37
Date
2012
Source
Nucleic acids research   40(5): 1916-1927 (Journal)
Registered Authors
Gómez-Skarmeta, José Luis
Keywords
none
MeSH Terms
  • Carrier Proteins/biosynthesis
  • Carrier Proteins/genetics
  • Cell Hypoxia
  • Cell Line
  • DNA Helicases/biosynthesis
  • DNA Helicases/genetics
  • DNA, Intergenic/chemistry
  • Gene Expression Regulation*
  • Gene Silencing
  • Glycogen Synthase/genetics
  • Humans
  • Insulator Elements*
PubMed
22067454 Full text @ Nucleic Acids Res.
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.

Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping