EPAS1 and nonpapillary renal cell carcinoma: Remarkably, the effects on HIF-2α target gene expression were paralleled by disruptions of HIF-2α speckle targeting abilities and differential ccRCC patient speckle signature (Fig 4H-I), supporting that disruption of DNA-speckle contacts or changes in speckles can shift the types of genes that are preferentially activated by a transcription factor.