Zinc Finger Protein 451 is a novel Smad corepressor in Transforming Growth Factor-{beta} signaling [Gene Regulation]

December 9th, 2013 by Feng, Y., Wu, H., Xu, Y., Zhang, Z., Liu, T., Lin, X., Feng, X.-H.

Zinc Figure Protein 451 (ZNF451) is a transcriptional cofactor localized to promyelocytic leukemia (PML) bodies. Here, we present evidence demonstrating that ZNF451 physically interacts with Smad3/4 and functionally inhibits TGF-β signaling. Increased expression of ZNF451 attenuates TGF-β-induced growth inhibitory and gene transcriptional responses, whereas depletion of ZNF451 enhances TGF-β responses. Mechanistically, ZNF451 blocks the ability of Smad3/4 to recruit p300 in response to TGF-β, which causes reduction of histone H3K9 acetylation on the promoters of TGF-β target genes. Taken together, ZNF451 acts as a transcriptional corepressor for Smad3/4 and negatively regulates TGF-β signaling.