Members of the Jumonji domain 2 (JMJD2) family contain a JmjN domain, a JmjC domain, a JD2H domain, two TUDOR domains, and two PHD-type zinc fingers. Like other members of the JMJD1 and JMJD2 families, JMJD2B is a histone demethylase, but is reported to be a very poor enzyme. Similar to JMJD1A, JMJD2B is a transcriptional target of the hypoxia-inducible factor (HIF), and hypoxic cells express elevated levels of the JMJD2B mRNA and protein. Both JMJD1A and JMJD2B retain their histone demethylase activity in hypoxic conditions, suggesting that this activity of JMJD2B might play a role in the hypoxic gene expression program.