Differential sub-nuclear distribution of hypoxia-inducible factors (HIF)-1 and -2 alpha impacts on their stability and mobility. Issue 9 (September 2016)

• Record Type: Journal Article
• Authors: Taylor, S. E.; Bagnall, J.; Mason, D.; Levy, R.; Fernig, D. G.; See, V.
• Is Part Of: Open biology. Volume 6:Issue 9(2016)
• Publication Date: 2016-09
• Subjects: hypoxia -- hypoxia-inducible factor -- HIF-2α -- nuclear speckles -- confocal microscopy -- fluorescence recovery after photo-bleaching; Biology -- Periodicals; 570
• DOI: 10.1098/rsob.160195
• Languages: English
• ISSNs: 2046-2441

Abstract

Abstract : Cellular adaptation to hypoxia occurs via a complex programme of gene expression mediated by the hypoxia-inducible factor (HIF). The oxygen labile alpha subunits, HIF-1α/-2α, form a heterodimeric transcription factor with HIF-1β and modulate gene expression. HIF-1α and HIF-2α possess similar domain structure and bind to the same consensus sequence. However, they have different oxygen-dependent stability and activate distinct genes. To better understand these differences, we used fluorescent microscopy to determine precise localization and dynamics. We observed a homogeneous distribution of HIF-1α in the nucleus, while HIF-2α localized into speckles. We demonstrated that the number, size and mobility of HIF-2α speckles were independent of cellular oxygenation and that HIF-2α molecules were capable of exchanging between the speckles and nucleoplasm in an oxygen-independent manner. The concentration of HIF-2α into speckles may explain its increased stability compared with HIF-1α and its slower mobility may offer a mechanism for gene specificity.