A novel subfamily of zinc finger genes involved in embryonic development

Abstract

C2H2 zinc finger proteins make up one of the largest protein families in eukaryotic organisms. Recent study in several different systems has identified a set of novel zinc finger proteins that appear to form a distinct subfamily that we have named the NET family. Members of the NET family (Noc, Nlz, Elbow, and Tlp-1) share two protein motifs--a buttonhead box and an Sp motif--with zinc finger proteins from the Sp family. However, the NET family is uniquely characterized by a single atypical C2H2 zinc finger, in contrast to the Sp family that contains three tandem C2H2 fingers. Here, we review current information about the biochemical function and in vivo role for members of this subfamily. In general, NET family proteins are required during embryonic development. They appear to act by regulating transcription, most likely as repressors, although they are unlikely to bind DNA directly. In the future, it will be important to directly test if NET family proteins control transcription of specific target genes, perhaps via interactions with DNA-binding transcription factors, as well as to further explore their function in vivo.

Zfra affects TNF-mediated cell death by interacting with death domain protein TRADD and negatively regulates the activation of NF-κB, JNK1, p53 and WOX1 during stress response

“…We also determined that absent expression of Zfra is found in several breast and prostate cancer cell lines [10], implying that Zfra deficiency may provide a growth advantage for cancer cells. Majority of zinc finger proteins participate in gene transcription and embryonic development [30-32]. Synthetic peptides have been shown promises in therapy to modulate the transcriptional activities of endogenous zinc finger proteins [33,34].…”

Zeppo1 is a novel metastasis promoter that repressesE-cadherinexpression and regulates p120-catenin isoform expression and localization

“…Zpo1 is a member of the NET (Noc/Nlz, Elbow, and Tlp-1) family of proteins (Nakamura et al 2004) that function in embryonic development in zebrafish (Hoyle et al 2004;Brown et al 2009), Drosophila (Dorfman et al 2002), and Caenorhabditis elegans (Zhao et al 2002). We show here that Zpo1 functions as a transcriptional repressor.…”

Ancient duplicated conserved noncoding elements in vertebrates: A genomic and functional analysis

“…The remaining 13 families were located close to five single pairs of paralogous genes (NRXN1/NRXN3, ZNF521/ZNF423, ZNF503/ ZNF703, ODZ3/ODZ4, and DLG1/DLG2) that were not considered trans-dev by our criteria. It is interesting to note, however, that orthologs of these genes have evidence to suggest they are implicated in development: NRXN1/NRXN3, ZNF521/ZNF423, and ZNF503/ZNF703 all have known mammalian developmental roles (Püschel and Betz 1995;Tsai and Reed 1998;Bond et al 2004;Chang et al 2004;Nakamura et al 2004); the Drosophila odz gene, a homolog of mammalian ODZ3/ODZ4, is a pair-rule gene with many patterning roles throughout development (BenZur et al 2000); and DLG1 and DLG2, two relatively uncharacterized synapse-associated genes, have a close paralog, DLG3, that is known to be expressed in early brain development (Tarpey et al 2004). Therefore, given their proven or probable developmental roles, as well as their status as the only close paralogs in the vicinity, we included these five pairs in our set of likely target genes for further analysis.…”