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

Taylor, SE, Bagnall, J, Mason, D ORCID: 0000-0002-8773-5274, Levy, R ORCID: 0000-0001-5728-0531, Fernig, DG ORCID: 0000-0003-4875-4293 and See, V ORCID: 0000-0001-6384-8381 (2016) Differential sub-nuclear distribution of hypoxia-inducible factors (HIF)-1 and-2 alpha impacts on their stability and mobility. OPEN BIOLOGY, 6 (9). 160195-.

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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.

Item Type:	Article
Uncontrolled Keywords:	hypoxia, hypoxia-inducible factor, HIF-2 alpha, nuclear speckles, confocal microscopy, fluorescence recovery after photo-bleaching
Depositing User:	Symplectic Admin
Date Deposited:	07 Oct 2016 15:21
Last Modified:	19 Jan 2023 07:29
DOI:	10.1098/rsob.160195
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3003678