Cells are often exposed to hypoxic condition in microenvironment of our body. Hypoxic condition induces various adaptive responses including alteration of metabolism, respiration, and cell growth. Furthermore, hypoxia induces malignant transformation of cancer cells, and promotes invasion and metastasis. Hypoxia-Inducible Factor (HIF) is a transcription factor which plays a key role in hypoxic response by inducing expression of multiple genes. Previously, we have demonstrated that HIF is activated upon early phase of hypoxic condition, whereas CREB becomes activated during late phase of hypoxia when HIF is downregulated.
In addition to transcription factors, chromosome conformation is a critical factor to determine the gene expression status. To understand the significance of higher order genome organization in the regulation of hypoxic gene expression, we have performed a large scale nuclear gene position analysis of hypoxia-responsive genes. Using high-throughput imaging, radial and relative nuclear positions of more than 100 HIF- and CREB-target genes were mapped in 3D space under hypoxic condition. We find that that some genes changed their nuclear positions and their relative positions to each other in response to hypoxic treatment for 48 h whereas others did not. However, no pervasive correlation between the distance and gene expression was observed. Possible roles of gene repositioning under hypoxic condition will be discussed.