Cloning And Function Analysis Of Novel Human Heart Development Candidate Gene ZNF446

To a large extent, cellular differentiation is regulated by transcription factors. Several larger families of transcription factors have been identified, and in mammals, zinc finger proteins probably constitute the largest individual family of such nucleic acid - binding proteins. In the present study, we report the identification and characterization of a novel KRAB~containing zinc-finger protein, ZNF446,; from a human embryonic heart cDNA library, ZNF446 encodes a putative protein of 450 amino acids. The protein is conserved across different species during evolution. Northern blot analysis indicates that ZNF446 is expresses in heart, liver, placenta, muscles, and pancreas and in a very embryonic development-specific stage of human tissue stomach. In COS-7 cells, ZNF446 protein is localized to nucleus. ZNF446 is a transcription repressor by KKA13 motif when fused to Gal-4 DNAHbinding domain and cotranfected with VP-16. Overexpression of ZNF446 in COS-7 cells inhibits the transcriptional activities of SRE and AP-1, suggesting that the ZNF44G protein may act as a transcriptional repressor in mitogen-activated protein kinase (MAPK) signaling pathway to mediate cellular...