The transcriptional activator ZNF143 is essential for normal development in zebrafish

Abstract

<p>Abstract</p> <p>Background</p> <p>ZNF143 is a sequence-specific DNA-binding protein that stimulates transcription of both small RNA genes by RNA polymerase II or III, or protein-coding genes by RNA polymerase II, using separable activating domains. We describe phenotypic effects following knockdown of this protein in developing <it>Danio rerio </it>(zebrafish) embryos by injection of morpholino antisense oligonucleotides that target znf143 mRNA.</p> <p>Results</p> <p>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 (<it>gata1</it>), cardiac myosin light chain 2 (<it>cmlc2</it>) and paired box gene 2a (<it>pax2a</it>). The zebrafish <it>pax2a </it>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.</p> <p>Conclusions</p> <p>Normal development of zebrafish embryos requires ZNF143. Furthermore, the <it>pax2a </it>gene is probably one example of many protein-coding gene targets of ZNF143 during zebrafish development.</p