Cloning And Functional Analysis Of A Novel Human Zinc Finger Gene ZNF328

The zinc finger proteins containing the Kruppel-associated box domain (KRAB-ZFPs) are the largest class of transcription factors in human genome. Many of the KRAB-ZFPs have been found to be involved in cardiac development or cardiovascular diseases. In this study, we have identified a novel human KRAB zinc finger gene, named ZNF328, from a human fetal heart cDNA library. The complete sequence of ZNF328 cDNA contains a 2376-bp open reading frame (ORF) and encodes a 792 amino acid protein with an N-terminal KRAB domain and classical zinc finger C₂H₂ motifs in the C-terminus. The gene consists of 8 exons, in which Exons 6 and 7 encode the KRAB domain A and B, respectively. ZNF328 is located in chromosome 19q13.4, encompassing genomic DNA of approximately 28 kb. ZNF328 is expressed in most of the human tissues analyzed in different developmental stages, suggesting a potential role of this gene in human embryonic development and related diseases. In the COS-7 cell, ZNF328 protein is expressed in nucleus. ZNF328 is a transcription suppressor when fused to Gal-4 DNA-binding domain and cotransfected with VP-16, KRAB motif is a potent repression domain. Overexpression of ZNF328 in COS-7 cells inhibits the transcriptional activities of SRE and AP-1, suggesting that the ZNF328 protein may act as a transcriptional repressor in mitogen-activated protein kinase (MAPK) signaling pathway to mediate cellular functions. In order...