Isolation and characterization of a novel member of the neural zinc finger factor/myelin transcription factor family with transcriptional repression activity

Abstract

Myelin transcription factor 1 (MyT1) and neural zinc finger factor 1 (NZF-1) represent the first two members of an emerging family of neural specific, zinc finger-containing DNA-binding proteins. MyT1 has been shown recently to play a critical role in neuronal cell differentiation during development. We have cloned the third member of the NZF/MyT family, referred to as neural zinc finger factor 3 (NZF-3). The cDNA sequence predicts a protein of 1,032 amino acids which contains two clusters of zinc fingers similar to MyT1 and NZF-1. Unlike MyT1 and NZF-1, NZF-3 does not contain an acidic domain at the amino terminus or a serine/threonine-rich region between the two finger clusters. NZF-3 binds to a DNA element containing a single copy of the previously described AAAGTTT consensus motif for these factors but exhibits a marked enhancement in relative affinity to a bipartite element containing two copies of the consensus motif. In contrast to MyT1 and NZF-1, which are known to activate transcription, cotransfection experiments revealed that NZF-3 confers repression on the basal activity of promoters containing the consensus binding elements. The identification of an additional member of the NZF/MyT family provides an opportunity to investigate the relative contribution of members of this family of transcription factors to the complex regulatory processes in neural development and homeostasis.