The nuclear localization of SWI/SNF proteins is subjected to oxygen regulation

To identify regulatory proteins that play a causal role in mediating hypoxia responses, we characterized the time courses of relocalization of hypoxia-altered nuclear proteins in response to hypoxia and reoxygenation. We found that 17 nuclear proteins relocalized in a significantly shorter time period in response to both hypoxia and reoxygenation. Particularly, several components of the SWI/SNF complex were fast responders, and analysis of gene expression data show that many targets of the SWI/SNF proteins are oxygen regulated. Furthermore, confocal fluorescent live cell imaging showed that over 95% of hypoxia-altered SWI/SNF proteins accumulated in the cytosol in hypoxic cells, while over 95% of the proteins were nuclear in normoxic cells, as expected.SWI/SNF proteins relocalize in response to hypoxia and reoxygenation in a quick manner, and their relocalization likely accounts for, in part or in whole, oxygen regulation of many SWI/SNF target genes.Living organisms ranging from yeast to mammals use oxygen to generate their cellular energy supply and to synthesize important biomolecules. Hence, they need to respond effectively to changes in oxygen levels in the environment, particularly to hypoxia [1,2]. In humans, hypoxia is responsible for death or damage by the ischemia accompanying heart attack, stroke, and traumatic injuries [3-5]. The molecular and cellular events induced by changes in oxygen levels are very broad in eukaryotes. For example, over 20% of yeast genes change their transcript levels in response to hypoxia [6]. In the human arterial endothelial cells, more than 8% of all genes alter their transcript levels by at least 1.5-fold in response to hypoxia [7]. In the human primary astrocytes, more than 5% of the genes alter their transcript levels by at least 2-fold in response to hypoxia [8]. Such broad changes in gene expression likely involve coordinated actions of multiple pathways and regulators.Previous studies have identified several transcriptio