Tantalus, a Novel ASX-Interacting Protein with Tissue-Specific Functions

Abstract

The Drosophila trithorax- and Polycomb-group (trxG and PcG) proteins maintain activated and repressed transcriptional states at specific target gene loci. The Additional sex combs (Asx) gene is of particular interest as it appears to function in both protein complexes and yet its effects on target genes are more restricted. A novel protein, Tantalus (TAN), was identified in a yeast two-hybrid screen for ASX-interacting proteins that might confer tissue-specific ASX functions. TAN contains consensus nuclear localization sites and binds DNA in vitro. However, its subcellular localization varies in a tissue-specific fashion. In salivary glands, TAN is predominantly nuclear and associates with 66 euchromatic sites on polytene chromosomes, more than half of which overlap with ASX. These loci do not include the homeotic genes of the ANT and BX complexes bound by other PcG and trxG proteins. Rather, tan mutant defects are restricted to sensory organs. We show that one of these defects, shared by Asx, is genetically enhanced by Asx. Taken together, the data suggest that TAN is a tissue-specific cofactor for ASX, and that its activity may be partially controlled by subcellular trafficking.

The HARE-HTH and associated domains

“…This suggests that if the interaction between the ASXL proteins and Calypso/BAP1-like proteins is indeed mediated by the ASXH domain, then it might be an animal-specific feature of the domain. Another potential animal-specific binding partner of the ASXL proteins is prototyped by the Drosophila Tantalus protein, 34 whose orthologs we identified for the first time in other metazoans (Sup. Material).…”

“…In this regard, recent studies have shown that ASXL1, one of the three human orthologs of the Drosophila Additional sex combs (Asx) gene, [30][31][32][33] an enhancer of both the polycomb and trithorax group genes, 34 is a major target of mutations leading to myeloproliferative and myelodysplastic conditions, including acute myeloid leukemia, polycythemia vera, essential thrombocythemia and primitive myelofibrosis. 24,[35][36][37][38][39][40] ASXL1 mutations along with those in another polycomb group gene EZH2 are also indicative of poor overall survival in patients with myelodysplastic syndromes, independent of other known risk factors.…”

tantalus, a potential link between Notch signalling and chromatin-remodelling complexes

“…All tan lines and constructs used here have been described previously (Dietrich et al 2001), and Gal4 driver lines used are described in Flybase (http://flystocks.bio.indiana.edu/ gal4.htm). The loss-of-function allele N 8 and the hypomorphic allele N 55e11 (described in Flybase) were crossed to either tan 2 homozygotes or P[tan];tan 2 homozygotes and the number of flies with four or fewer interocellar bristles were counted.…”

“…Although tan is expressed throughout embryogenesis and larval development, higher levels of expression are observed in some tissues (e.g. the morphogenetic furrow of the eye disc; Dietrich et al 2001). Flies homozygous for tan null mutations exhibit a variety of sensory organ defects including roughened eyes, bristle loss and duplication and minor defects in distal wing vein formation, but are otherwise viable and fertile.…”

“…The tantalus (tan) gene was identified in a yeast twohybrid screen designed to uncover interactors for the Polycomb and trithorax group (Pc-G and trx-G) protein Additional sex combs (ASX; Dietrich et al 2001). The Pc-G and trx-G protein complexes act to maintain states of transcription during development in a wide range of organisms (reviewed in Orlando 2003).…”