Zinc finger protein 451 is a novel Smad corepressor in transforming growth factor-ß 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-ß signaling. Increased expression of ZNF451 attenuates TGF-ß-induced growth inhibitory and gene transcriptional responses, whereas depletion of ZNF451 enhances TGF-ß responses. Mechanistically, ZNF451 blocks the ability of Smad3/4 to recruit p300 in response to TGF-ß, which causes reduction of histone H3K9 acetylation on the promoters of TGF-ß target genes. Taken together, ZNF451 acts as a transcriptional corepressor for Smad3/4 and negatively regulates TGF-ß signaling.