Studies On Cloning, Expression And Function Of Human Zinc Finger Protein Novel Gene ZNF394

Zinc-finger (ZF) proteins are widely distributed in the eukaryoty. Identification of regulatory genes in cardiovascular system is necessary in our understanding of the pathogenesis of congenital heart defects (CHD) and acquired cardiovascular diseases. The Cys2/His type zinc finger genes are the single largest class of transcription factors in the human genome, and some of them have been found to be involved in cardiac development or cardiovascular diseases.With the aim of identifying the genes involved in human heart development and disease, we have isolated a novel SCAN(LER)-related zinc finger gene from heart cDNA library. The gene is named ZNF394 and its name has been approved by Human Genome Organization(HUGO). The cDNA sequence contains an open reading frame of 1686 bp, encoding a putative protein of 516 amino acid residues with a predicted molecular mass of 64 kDa. The ZNF394 gene is mapped to chromosome 7q11.21. The N-terminus of the ZNF394 coding region has a well-conserved Kruppel-associated box (KRAB) domain and adjacent to an ami no-terminal SCAN domain (or leucine-rich region), whereas the C-terminus contains 7 CsHz zinc finger motifs in tandem arrays with the highly conserved space region of the H/C-link. Northern blot analysis indicates that a 2. 18 kb transcript specific for ZNF394 is expressed in the heart, brain and skeletal muscle of adult stage. Immunochemistry analysis with polyclone antibody against ZNF394shows that the expression of ZNF394 protein is in the heart, limb bud, and dorsal neural tube in embryo tissues. The fusion protein made between ZNF394 and GFP was detected at a high level in the nuclei of COS-7 cells. Overexpression of ZNF394 in the cell inhibits the transcriptional activities of C-Jun and AP-1 genes. These results suggest that ZNF394 may be a transcriptional represser in Mitogen-activated protein kinase (MAPK) signal transduction pathways and may play important roles in cardiac development and/or cardiac function.