Abstracts of the “8th Int. Luebeck Conference Pathophysiology and Pharmacology of Erythropoietin and Other Hemopoietic Growth Factors” (pages E1–E30)

摘要

sequence called HRE (hypoxia-responsive element). Studies with gene manipulated mouse lines revealed that the is dispensable for gene expression in the kidney. Additionally, we found that histones in the Epo promoter region areacetylated in unstressed normal liver. This indicates that the promoter region is epigenetically initialized and acquirescompetent status for immediate induction of gene expression under hypoxic conditions. Interestingly, this promoter regulation of the hypoxia responsive genes. To elucidate chromatin dynamics during HIF-mediated transcriptionalactivation, positioning of HIF and nucleosome in the chromosome were examined using HRE-containing promotersfrom the CA9 and PGK1 genes as model systems. Chromatin immunoprecipitation (ChIP) analyses of human cell to hypoxia. The nucleosome positioning in the promoters were investigated using a chromatin reassembly system infrog (Xenopus laevis) oocytes. As assessed by endonuclease-sensitivity assays of the reassembled chromatin, the molecular mechanism linking HIF-mediated chromatin dynamics to hypoxia-inducible transcriptional activation.