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Figure 3: Multiple Signaling Pathways Regulate HIF Function and Key Determinants of the Transcription Activity of HIF-1 and HIF-2. The overall function of HIF complexes is mainly determined by protein levels of the α-subunits (HIF-α) and their interactions with p300 or CBP. Multiple signaling pathways may modulate HIF function either through acting on HIF-α (stability or simple posttranslational modifications) or on p300/CBP (posttranslational modifications). Eventually, the HIF-α-p300 or HIF-α-CBP complexes serve as the integrators of these signals and coordinate the dynamic reprogramming of gene expression. HDACs may directly interact with the HIF transcription complexes, or indirectly or functionally interact with these signaling pathways and regulate HIF function.