REST mediates resolution of HIF-dependent gene expression in prolonged hypoxia

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

Architecture, symbolic capital and elite mobilizations: The case of the Royal Bank of Scotland corporate campus

In this article, we apply the conceptual framework of Pierre Bourdieu, in particular forms of capital, social fields, field of power and modes of domination, to demonstrate how the study of a symbolically powerful building can provide insights into what are often opaque elite interactions. In order to do this, we focus on the corporate campus headquarters of a powerful financial institution, the Royal Bank of Scotland in the context of Scotland in the period 2000–2009. We pose the following questions: What is the relationship between corporate space and the field of power? What role does a corporate building play in circuits of capital conversion? What does this case tell us about the role of architecture in elite mobilisations? In addressing these questions, we contribute to critical organisation studies by identifying and theorising the role of corporate space in inter-elite dynamics and circuits of capital conversion. This approach, we argue, provides a methodological lever which could be applied to other symbolically important buildings in order to understand the nature and role of inter-field interactions in the conception and realisation of such buildings