title: [Epigenetics in kidney diseases].
abstract: Increasing evidence has demonstrated that chronic hypoxia in the tubulointerstitium results in irreversible chronic kidney diseases. Hypoxia inducible factor (HIF) is a transcriptional master regulator which takes control of gene expressions under hypoxia. Recently, HIF1 has been reported to organize a cluster of histone-modifying enzymes by binding to their promoter regions in various kinds of cell line. In order to clarify the epigenetic molecular mechanisms by HIF1, we examined the genome-wide analysis of HIF1-binding sites (ChIP-seq) in endothelial cells and HIF1 downstream target genes using DNA microarrays. ChIP-seq results demonstrated that HIF1 binds to the enhancer regions in addition to the promoter regions. We clarified that one of the HIF1 downstream genes, SLC2A3 (solute-carrier family 2A3, also known as glucose transporter 3: GLUT3), is regulated by changing chromosomal conformations under hypoxia via a cooperative combination of HIF1 and KDM3A(lysine(K) specific demethylase 3A), one of the histone demethylases. KDM3A is recruited to the SLC2A3 loci in an HIF1-dependent manner and demethylates histone repressive mark, H3K9me2, up-regulating its expression. In addition, we confirmed the interactions of HIF1 and KDM3A only under hypoxia using co-immunoprecipitation. These experimental results showed novel HIF1-dependent molecular mechanisms from an epigenetic viewpoint. It is important to elucidate the epigenetic mechanisms of chronic hypoxia in order to identify novel therapeutic approaches against chronic kidney disease.
authors.forename: Imari
authors.initials: I
authors.lastname: Mimura
authors.forename: Masaomi
authors.initials: M
authors.lastname: Nangaku
mesh_terms: D000818:Animals; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000235:genetics* / Q000502:physiology; D006657:Histones / Q000378:metabolism; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones; D014157:Transcription Factors; D010100:Oxygen