Visualization of the three-dimensional organization of hypoxia-inducible factor-1α and interacting cofactors in subnuclear structures

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Abstract
Cells need oxygen (O2) to meet their metabolic demands. Highly efficient systems of O2-sensing have evolved to initiate responses enabling cells to adapt their metabolism to reduced O2 availability. Of central importance is the activation of hypoxiainducible factor-1 (HIF-1), a transcription factor complex that controls the expression of genes the products of which regulate glucose uptake and metabolism, vasotonus and angiogenesis, oxygen capacity of the blood as well as cell growth and death. Activation of HIF-1 requires the accumulation and nuclear translocation of the HIF-1α subunit, its dimerization with HIF-1β and the binding of coactivator proteins such as p300. In this study we investigated the threedimensional (3D) distribution of HIF-1α within the nucleus and assigned its localization to known nuclear compartments. Using twophoton microscopy we determined the colocalization of HIF-1α and -β subunits within nuclear domains as well as overlaps between HIF-1α and p300. Our data provide information on the nuclear distribution of HIF-1α with respect to subnuclear domains that could serve as specific locations for hypoxiainduced gene expression.

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