FIG 11.

Schematic diagram showing how Jmjd1a and G9a modulate hypoxia signaling pathways in normal and germ cell-derived tumor development. HIFs directly activate Jmjd1a transcription, and some of the HIFs also target genes responsible for the induction of angiogenesis, such as Adm in the acute phase. However, in the later stages (chronic hypoxia), Jmjd1a derepresses expression of antiangiogenic factors as a negative-feedback mechanism to prevent excess vascular formation. In contrast, G9a is upregulated during acute hypoxia and suppresses apoptosis in the chronic hypoxia phase (upper panel). In the absence of Jmjd1a, the induction of antiangiogenic factors is lost or severely attenuated, leading to excess vascular formation. This may facilitate the maintenance of immature, stem cell-like tumor populations that eventually lead to tumor development (lower panel).