| Type: | Family | Name: | Nervy |
| Description: | Transcriptional activation and repression is required for control of cell proliferation and differentiation during embryonic development and homeostasis in the adult organism. Perturbations of these processes can lead to the development of cancer []. The Eight-Twenty-One (ETO) gene product is able to form complexes with corepressors and deacetylases, such as nuclear receptor corepressor (N-CoR), which repress transcription when recruited by transcription factors []. The ETO gene derives its name from its association with many cases of acute myelogenous leukaemia (AML), in which a reciprocal translocation, t(8;21), brings together a large portion of the ETO gene from chromosome eight and part of the AML1 gene from chromosome 21. The human ETO gene family currently comprises three major subfamilies: ETO/myeloid transforming gene on chromosome 8 (MTG8); myeloid transforming gene related protein-1 (MTGR1) and myeloid transforming gene on chromosome 16 (MTG16). ETO proteins are composed of four evolutionarily conserved domains termed nervy homology regions (NHR) 1-4. NHR1 is thought to stabilise the formation of high molecular weight complexes, but is not directly responsible for repressor activity. NHR2 and its flanking sequence comprise the core repressor domain, which mediates 50% of the wild type repressor activity. Furthermore, there is evidence that the amphipathic helical structure of NHR2 promotes the formation of ETO/AML1 homodimers []. NHR3 and NHR4 have been shown to act in concert to bind N-CoR. NHR4 contains two zinc finger motifs, which are thought to play a role in protein interactions rather than DNA binding []. The ultrabithorax (Ubx) gene is a homeotic gene in Drosophila that determines the morphological characteristics of each segment. Ubiquitous expression of Ubx gave rise to increased expression of several mRNAs; one of these transcripts was localised to the nervous system precursor cells of the head, thoracic and abdominal segments, and was termed nervy. Analysis of nervy cDNA revealed that it shared significant sequence similarity with the human ETO gene; it was also found to contain a region of similarity to the TATA binding protein-associated factor TAF110 []. | Short Name: | Nervy |
