The transcriptional activator ZNF143 is essential for normal development in zebrafish

The loss of function phenotype is pleiotropic and includes a broad array of abnormalities including defects in heart, blood, ear and midbrain hindbrain boundary. Defects are rescued by coinjection of synthetic mRNA encoding full-length ZNF143 protein, but not by protein lacking the amino-terminal activation domains. Accordingly, expression of several marker genes is affected following knockdown, including GATA-binding protein 1 (gata1), cardiac myosin light chain 2 (cmlc2) and paired box gene 2a (pax2a). The zebrafish pax2a gene proximal promoter contains two binding sites for ZNF143, and reporter gene transcription driven by this promoter in transfected cells is activated by this protein.Normal development of zebrafish embryos requires ZNF143. Furthermore, the pax2a gene is probably one example of many protein-coding gene targets of ZNF143 during zebrafish development.The vertebrate transcriptional activator protein, ZNF143 (also known as STAF for selenocysteine tRNA gene transcription activating factor, or SBF for SPH-binding factor) operates at a multitude of small RNA and protein-coding gene promoters [1-5]. Two separable activation domains within this protein stimulate transcription selectively at either small RNA or mRNA promoters [6]. Initially, attention was focused on the function of ZNF143 for small RNA gene transcription, especially for vertebrate snRNA and selenocysteine tRNA genes [7-9]. Then, several mRNA genes were identified whose proximal promoters contained SPH sites [10-15]. Possibly because of the highly degenerate and relatively long DNA-binding site recognized by ZNF143, it was not recognized for many years that approximately 2000 mammalian protein-coding genes contain SPH (SphI Postoctamer Homology [16]) elements, or STAF Binding Sites (SBS), in their promoters [5].Little is known concerning the phenotypic role(s) of ZNF143 during cellular growth and animal development. A number of cell-cycle-associated gene promoters are regulated by ZNF143 [