The histone demethylase Jumonji domain containing 1A (JMJDIA) demethylates H3K9 residues and thereby transactivates distinct target genes. Investigating the effect of hypoxia on JMJDIA expression, we found increased JMJDIA mRNA in different organs of rats exposed to normobaric hypoxia (8% O-2). Compared to adult samples, JMJDIA was increased in most tissues of human fetuses in whom oxygen supply is low compared to postnatal levels. Upregulation of JMJDIA mRNA and protein in cultured human cells exposed to hypoxia or iron scavengers in vitro was abrogated when hypoxia-inducible factor-1 (HIF-1) signaling was blocked by siRNAs. A single pivotal hypoxia responsive element (HRE) in the promoter of the human JMJDIA gene was identified that mediates JMJDIA upregulation by hypoxia, iron scavengers, and HIF-1. These findings demonstrate that JMJDIA can be stimulated by hypoxia both in vitro and in vivo involving binding of HIF-1 to a specific HRE in the JMJDIA promoter. (c) 2008 Elsevier Inc. All rights reserved.