Disease relevance of tin

• Expression of HOX homeogenes in human neuroblastoma cell culture lines [1].
• Expression of HOX homeobox genes in the adult human colonic mucosa (and colorectal cancer?) [2].
• We studied the expression of 33 human homeobox genes belonging to four complex HOX loci in embryonal carcinoma NT2/D1 cells [3].

High impact information on tin

• Taspase1: a threonine aspartase required for cleavage of MLL and proper HOX gene expression [4].
• An early and important event in the regional subdivision of the mesoderm is the restriction of tinman expression to dorsal mesodermal cells [5].
• Early in Drosophila embryogenesis, gap gene products directly repress transcription of homeotic (HOX) genes and thereby delimit HOX expression domains [6].
• Polycomb response elements (PREs) are specific cis-regulatory sequences needed for transcriptional repression of HOX and other target genes by Polycomb group (PcG) proteins [7].
• The linear arrangement of the Hox genes on the chromosome correlates with the spatial distribution of HOX protein expression along the anterior-posterior axis of the embryo [8].

Biological context of tin

• We show that an evolutionarily conserved bap enhancer element requires combinatorial binding sites for Tin and Dpp-activated Smad proteins for its activity [9].
• We demonstrate further that a mesodermally active enhancer of eve contains several Smad and Tin binding sites that are essential for enhancer activity in vivo [10].
• The Drosophila homeobox gene tinman plays a critical role in subdividing the early mesoderm [11].
• In Drosophila, induction of visceral mesoderm, dorsal muscles, and the heart by Dpp is, at least in part, effected through the transcriptional activation and function of the homeobox gene tinman in dorsal mesodermal cells during early embryogenesis [12].
• The homeotic proteins encoded by the genes of the Drosophila HOM and the vertebrate HOX complexes do not bind divergent DNA sequences with a high selectivity [13].

Anatomical context of tin

• We show that the binding and synergistic activities of Smad and Tinman proteins are critical for mesodermal tinman induction, whereas repressor binding sites prevent induction in the dorsal ectoderm and amnioserosa [12].
• We identified a cis-regulatory element in the first intron of dSUR, which contains Tinman consensus binding sites and is sufficient for faithful dSUR expression in the fly's myocardium [14].
• Both Tin binding sites are required for enhancer activity in all three muscle cell lineages [15].
• Several vertebrate relatives of tinman, many of which are predominately expressed in the very early cardiac progenitors (and pharyngeal endoderm), also seem to promote heart development [16].
• We have previously described CEH-22, an NK-2 class homeodomain transcription factor similar to Drosophila tinman and vertebrate Nkx2-5, which is expressed exclusively in the pharyngeal muscles [17].

Associations of tin with chemical compounds

• These include sets of four cell pairs that express the homeodomain protein Tinman (Tin), alternating with groups of two cell pairs that express the orphan steroid hormone receptor Seven Up (Svp) [18].
• HOX gene activation by retinoic acid [19].
• Spontaneous and bleomycin-induced genomic alterations in the progeny of Drosophila treated males depends on the Msh2 status. DNA fingerprinting analysis [20].

Physical interactions of tin

• Thus, these two Tinman binding sites act in concert to drive beta3 tubulin gene expression during heart development [21].

Regulatory relationships of tin

• tincar encodes a novel transmembrane protein expressed in the Tinman-expressing cardioblasts of Drosophila [22].
• Conversely, ectopic expression of ush results in a decrease in the number of cardioblasts in the heart and the inhibition of a cardial cell enhancer normally regulated by the synergistic activity of the Pannier and Tinman cardiogenic factors [23].
• Tinman regulates the transcription of the beta3 tubulin gene (betaTub60D) in the dorsal vessel of Drosophila [21].

Other interactions of tin

• By contrast, pan-mesodermal overexpression of pannier ectopically expands tinman expression, whereas overexpression of u-shaped inhibits cardiogenesis [24].
• We propose that nmr is another determinant of cardiogenesis, along with tinman and pannier [25].
• The tinc mRNA was expressed specifically in four of the six pairs of cardioblasts in each segment, in a pattern identical to that of tinman (tin), a homeobox gene required for the specification of the dorsal vessel [22].
• The patterns of wingless, decapentaplegic, and tinman position the Drosophila heart [26].
• Conversely, the expression of the Dorsocross (Doc) T-box genes, which is normally restricted to the two Tin-negative cardioblasts in each hemisegment, is strongly expanded into the majority of cardioblasts in mid mutant and mid+H15-deficient embryos [27].

Analytical, diagnostic and therapeutic context of tin

• Here we present a functional dissection of a tinman enhancer that mediates the Dpp response [12].
• Site-directed mutagenesis of this element shows that these Tinman sites are critical to dSUR expression, and further genetic manipulations suggest that the GATA transcription factor Pannier is synergistically involved in cardiac-restricted dSUR expression in vivo [14].
• We have isolated a new homeobox-containing gene, msh-2, by means of the polymerase chain reactions (PCR) using redundant primers. msh-2 is specifically expressed in mesodermal primordia during a short time period early in development [28].
• Using immunoprecipitation and in vitro pull-down assays, we show that NK-4 directly interacts with the Groucho corepressor, for which the homeodomain is required [29].
• Development of the Drosophila embryonic midgut is dependent on a number of genes, including tinman and bagpipe, which are required for formation of the visceral mesoderm, and the homeotic genes and their targets, which act locally in the visceral mesoderm to direct formation of specific midgut constrictions [30].

References