Dynamic Change of Chromatin Conformation in Response to Hypoxia Enhances the Expression of GLUT3 (SLC2A3) by Cooperative Interaction of Hypoxia-Inducible Factor 1 and KDM3A

• DOI: 10.1128/mcb.06643-11
• Publication Date: 2012-05-30T03:57:16Z
• Authors: Imari Mimura; Masaomi Nangaku; Yasuharu Kanki; Shuichi Tsutsumi; Tsuyoshi Inoue; Takahide Kohro; Shogo Yamamoto; Takanori Fujita; Teppei Shimamura; Jun-ichi Suehiro; Akashi Taguchi; Mika Kobayashi; Kyoko Tanimura; Takeshi Inagaki; Toshiya Tanaka; Takao Hamakubo; Juro Sakai; Hiroyuki Aburatani; Tatsuhiko Kodama; Youichiro Wada
• Keywords: Chromatin immunoprecipitation; Hypoxia-Inducible Factors

Hypoxia-inducible factor 1 (HIF1) is a master regulator of adaptive gene expression under hypoxia. However, role for HIF1 in the epigenetic regulation remains unknown. Genome-wide analysis binding sites (chromatin immunoprecipitation [ChIP] with deep sequencing) endothelial cells clarified that mainly binds to intergenic regions distal from transcriptional starting both normoxia and Next, we examined temporal profile hypoxic conditions by using DNA microarrays. We early hypoxia-responsive genes are functionally associated glycolysis, including GLUT3 (SLC2A3). Acetylated lysine 27 histone 3 covered sites, functioned as an enhancer SLC2A3 interaction (K)-specific demethylase 3A (KDM3A). Knockdown HIF1α KDM3A showed glycolytic regulated respond hypoxia manner independent cell type specificity. elucidated chromatin conformational structure modification change enhance based on combined results conformation capture (3C) ChIP assays. recruited locus HIF1-dependent demethylates H3K9me2 so upregulate its expression. These findings provide novel insights into between also HIF1.