Zinc Finger Protein 451 Is a Novel Smad Corepressor in Transforming Growth Factor-β Signaling

ZNF451 is a transcriptional cofactor localized to promyelocytic leukemia bodies. Here, we present evidence demonstrating that ZNF451 physically interacts with Smad3/4 and functionally inhibits TGF- signaling. Increased expression of ZNF451 attenuates TGF--induced growth inhibitory and gene transcriptional responses, whereas depletion of ZNF451 enhances TGF- responses. Mechanistically, ZNF451 blocks the ability of Smad3/4 to recruit p300 in response to TGF-, which causes reduction of histone H3K9 acetylation on the promoters of TGF- target genes. Taken together, ZNF451 acts as a transcriptional corepressor for Smad3/4 and negatively regulates TGF- signaling.