In vivo and in vitro approaches to identify the molecular and neurodevelopmental function of Zfp536

Abstract

Zfp536 is a zinc finger protein predominantly expressed in developing central nervous system. Recent genome-wide association studies have identified Zfp536 as one of the schizophrenia-associated genetic loci. In zebrafish, it has been shown that Zfp536 functions as a transcription factor implicated in social behavior and stress. However, its function in developing brain is not well studied yet. We have adopted systematic approaches to examine the functions of Zfp536 as a transcription factor in developing brain. First, we have generated Zfp536 knockout mouse line using CRISPR-Cas9 by the introduction of a frameshift mutation in exon 3 causing early termination. Zfp536-/- mouse showed neonatal lethality suggesting its essential role during embryonic development. We are currently examined the neurodevelopmental defects of Zfp536-/- and the cause of their death. Second, we have generated human neuroblastoma cell line (IMR-32) expressing GFP-tagged ZNF536, a human homologue of mouse Zfp536. By ChIP-seq analysis, we aim to identify the genome-wide DNA binding sites which may reveal the function of Zfp536 as a transcription factor. Our approaches will reveal molecular functions of Zfp536 in developing brain.