Hypoxia upregulates the histone demethylase JMJD1A via HIF-1.
The histone demethylase Jumonji domain containing 1A (JMJD1A) demethylates H3K9 residues and thereby transactivates distinct target genes. Investigating the effect of hypoxia on JMJD1A expression, we found increased JMJD1A mRNA in different organs of rats exposed to normobaric hypoxia (8% O(2)). Compared to adult samples, JMJD1A was increased in most tissues of human fetuses in whom oxygen supply is low compared to postnatal levels. Upregulation of JMJD1A 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 JMJD1A gene was identified that mediates JMJD1A upregulation by hypoxia, iron scavengers, and HIF-1. These findings demonstrate that JMJD1A can be stimulated by hypoxia both in vitro and in vivo involving binding of HIF-1 to a specific HRE in the JMJD1A promoter.
Department of Neonatology, Basel University Children's Hospital Basel (UKBB), P.O. Box CH-4005, Basel, Switzerland. sven.wellmann@ukbb.ch
Sven
S
Wellmann
Maxi
M
Bettkober
Andrea
A
Zelmer
Karl
K
Seeger
Marion
M
Faigle
Holger K
HK
Eltzschig
Christoph
C
Bührer
D000693:Anaerobiosis / Q000235:genetics; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D005333:Fetus / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D056484:Jumonji Domain-Containing Histone Demethylases; D008745:Methylation; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014018:Tissue Distribution; D015854:Up-Regulation
D051793:Hypoxia-Inducible Factor 1; D012333:RNA, Messenger; D056484:Jumonji Domain-Containing Histone Demethylases; C530247:KDM3A protein, human; D010089:Oxidoreductases, N-Demethylating; D010100:Oxygen