Publication
REST mediates resolution of HIF-dependent gene expression in prolonged hypoxia
| dc.contributor.author | Cavadas, Miguel A. S. | |
| dc.contributor.author | Mesnieres, Marion | |
| dc.contributor.author | Crifo, Bianca | |
| dc.contributor.author | Manresa, Mario C. | |
| dc.contributor.author | Selfridge, Andrew C. | |
| dc.contributor.author | Scholz, Carsten C. | |
| dc.contributor.author | Cummins, Eoin P. | |
| dc.contributor.author | Cheong, Alex | |
| dc.contributor.author | Taylor, Cormac T. | |
| dc.date.accessioned | 2015-12-14T15:35:49Z | |
| dc.date.available | 2015-12-14T15:35:49Z | |
| dc.date.issued | 2015-12-09 | |
| dc.description.abstract | The hypoxia-inducible factor (HIF) is a key regulator of the cellular response to hypoxia which promotes oxygen delivery and metabolic adaptation to oxygen deprivation. However, the degree and duration of HIF-1α expression in hypoxia must be carefully balanced within cells in order to avoid unwanted side effects associated with excessive activity. The expression of HIF-1α mRNA is suppressed in prolonged hypoxia, suggesting that the control of HIF1A gene transcription is tightly regulated by negative feedback mechanisms. Little is known about the resolution of the HIF-1α protein response and the suppression of HIF-1α mRNA in prolonged hypoxia. Here, we demonstrate that the Repressor Element 1-Silencing Transcription factor (REST) binds to the HIF-1α promoter in a hypoxia-dependent manner. Knockdown of REST using RNAi increases the expression of HIF-1α mRNA, protein and transcriptional activity. Furthermore REST knockdown increases glucose consumption and lactate production in a HIF-1α- (but not HIF-2α-) dependent manner. Finally, REST promotes the resolution of HIF-1α protein expression in prolonged hypoxia. In conclusion, we hypothesize that REST represses transcription of HIF-1α in prolonged hypoxia, thus contributing to the resolution of the HIF-1α response. | pt_PT |
| dc.description.sponsorship | Science Foundation Ireland grant numnber: (06/CE/B1129). | pt_PT |
| dc.identifier.citation | Cavadas, M. A. S. et al. REST mediates resolution of HIF-dependent gene expression in prolonged hypoxia. Sci. Rep. 5, 17851; doi: 10.1038/srep17851 (2015). | pt_PT |
| dc.identifier.doi | 10.1038/srep17851 | pt_PT |
| dc.identifier.uri | http://hdl.handle.net/10400.7/533 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | Nature Publishing Group | pt_PT |
| dc.relation.publisherversion | http://www.nature.com/articles/srep17851 | pt_PT |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt_PT |
| dc.subject | Gene regulation | pt_PT |
| dc.subject | Transcriptional regulatory elements | pt_PT |
| dc.title | REST mediates resolution of HIF-dependent gene expression in prolonged hypoxia | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 12 | pt_PT |
| oaire.citation.startPage | 1 | pt_PT |
| oaire.citation.title | Scientific Reports | pt_PT |
| oaire.citation.volume | 5 | pt_PT |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |