A comparative genomic analysis of targets of Hox protein Ultrabithorax amongst distant insect species.
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ABSTRACT:
ORGANISM(S): Bombyx mori
PROVIDER: GSE71992 | GEO | 2016/07/27
SECONDARY ACCESSION(S): PRJNA292687
REPOSITORIES: GEO
Similar Datasets
Project description:In the fruitfly Drosophila melanogaster, the differential development of wing and haltere is dependent on the function of the Hox protein Ultrabithorax (Ubx). Here we compare Ubx-mediated regulation of wing patterning genes between the honeybee, Apis mellifera, the silkmoth, Bombyx mori and Drosophila. Orthologues of Ubx are expressed in the third thoracic segment of Apis and Bombyx, although they make functional hindwings. When over-expressed in transgenic Drosophila, Ubx derived from Apis or Bombyx could suppress wing development, suggesting evolutionary changes at the level of co-factors and/or targets of Ubx. To gain further insights into such events, we identified direct targets of Ubx from Apis and Bombyx by ChIP-seq and compared them with those of Drosophila. While majority of the putative targets of Ubx are species-specific, a considerable number of wing-patterning genes are retained, over the past 300?millions years, as targets in all the three species. Interestingly, many of these are differentially expressed only between wing and haltere in Drosophila but not between forewing and hindwing in Apis or Bombyx. Detailed bioinformatics and experimental validation of enhancer sequences suggest that, perhaps along with other factors, changes in the cis-regulatory sequences of earlier targets contribute to diversity in Ubx function.
| S-EPMC4906271 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-07-27 | E-GEOD-71992 | biostudies-arrayexpress
Project description:To gain insights into the species-specific events downstream of Ubx, we identified direct targets of Ubx from Apis by ChIP-seq and compared them with those of Drosophila at the level of both their function and regulation. While the majority of the targets are species-specific, the ontological distribution of all targets was similar amongst the two species. Interestingly, although considerable number of wing-patterning genes are retained as targets of Ubx over the past 300 millions years, many of them are differentially expressed only between wing and haltere in Drosophila and not between forewing and hindwing in Apis . Detailed bioinfomatics analysis and and experimental validation of enhancer sequences suggest that acquisition of binding sites for additional transcription factors without altering binding per se of Ubx could also contribute to the diversity in Ubx function.
2016-08-31 | GSE71847 | GEO
Project description:Hox proteins are transcription factors and key regulators of segmental identity along the anterior posterior axis across all bilaterian animals. Despite decades of research, the mechanisms by which Hox proteins select and regulate their targets remain elusive. We have carried out whole-genome ChIP-chip experiments to identify direct targets of Hox protein Ultrabithorax (Ubx) during haltere development in Drosophila. Direct targets identified include upstream regulators or cofactors of Ubx. Homothorax, a cofactor of Ubx during embryonic development, is one such target and is required for normal specification of haltere. Although Ubx bound sequences are conserved amongst various insect genomes, no consensus Ubx-specific motif was detected. Surprisingly, binding motifs for certain transcription factors that function either upstream or downstream to Ubx are enriched in these sequences suggesting complex regulatory loops governing Ubx function. Our data supports the hypothesis that specificity during Hox target selection is achieved by associating with other transcription factors.
| S-EPMC3244697 | biostudies-literature
Project description:Hox transcription factors are essential for shaping body morphology in development and evolution. The control of Hox protein activity in part arises from interaction with the PBC class of partners, pre-B cell transcription factor (Pbx) proteins in vertebrates and Extradenticle (Exd) in Drosophila. Characterized interactions occur through a single mode, involving a short hexapeptide motif in the Hox protein. This apparent uniqueness in Hox-PBC interaction provides little mechanistic insight in how the same cofactors endow Hox proteins with specific and diverse activities. Here, we identify in the Drosophila Ultrabithorax (Ubx) protein a short motif responsible for an alternative mode of Exd recruitment. Together with previous reports, this finding highlights that the Hox protein Ubx has multiple ways to interact with the Exd cofactor and suggests that flexibility in Hox-PBC contacts contributes to specify and diversify Hox protein function.
| S-EPMC2040397 | biostudies-literature
Project description:The Hox genes are responsible for generating morphological diversity along the anterior-posterior axis during animal development. The Drosophila Hox gene Ultrabithorax (Ubx), for example, is required for specifying the identity of the third thoracic (T3) segment of the adult, which includes the dorsal haltere, an appendage required for flight, and the ventral T3 leg. Ubx mutants show homeotic transformations of the T3 leg towards the identity of the T2 leg and the haltere towards the wing. All Hox genes, including Ubx, encode homeodomain containing transcription factors, raising the question of what target genes Ubx regulates to generate these adult structures. To address this question, we carried out whole genome ChIP-chip studies to identify all of the Ubx bound regions in the haltere and T3 leg imaginal discs, which are the precursors to these adult structures. In addition, we used ChIP-chip to identify the sites bound by the Hox cofactor, Homothorax (Hth). In contrast to previous ChIP-chip studies carried out in Drosophila embryos, these binding studies reveal that there is a remarkable amount of tissue- and transcription factor-specific binding. Analyses of the putative target genes bound and regulated by these factors suggest that Ubx regulates many downstream transcription factors and developmental pathways in the haltere and T3 leg. Finally, we discovered additional DNA sequence motifs that in some cases are specific for individual data sets, arguing that Ubx and/or Hth work together with many regionally expressed transcription factors to execute their functions. Together, these data provide the first whole-genome analysis of the binding sites and target genes regulated by Ubx to specify the morphologies of the adult T3 segment of the fly.
| S-EPMC3071676 | biostudies-literature
Project description:Hox genes encode a family of transcription factors that are key developmental regulators with a highly conserved role in specifying segmental diversity along the metazoan body axis. Although they have been shown to regulate a wide variety of downstream processes, direct transcriptional targets have been difficult to identify and this has been a major obstacle to our understanding of Hox gene function. We report the identification of genome-wide binding sites for the Hox protein Ultrabithorax (Ubx) using a YFP-tagged Drosophila protein-trap line together with chromatin immunoprecipitation and microarray analysis. We identify 1,147 genes bound by Ubx at high confidence in chromatin from the haltere imaginal disc, a prominent site of Ubx function where it specifies haltere versus wing development. The functional relevance of these genes is supported by their overlap with genes differentially expressed between wing and haltere imaginal discs. The Ubx-bound gene set is highly enriched in genes involved in developmental processes and contains both high-level regulators as well as genes involved in more basic cellular functions. Several signalling pathways are highly enriched in the Ubx target gene set and our analysis supports the view that Hox genes regulate many levels of developmental pathways and have targets distributed throughout the gene network. We also performed genome-wide analysis of the binding sites for the Hox cofactor Homothorax (Hth), revealing a striking similarity with the Ubx binding profile. We suggest that these binding profiles may be strongly influenced by chromatin accessibility and provide evidence of a link between Ubx/Hth binding and chromatin state at genes regulated by Polycomb silencing. Overall, we define a set of direct Ubx targets in the haltere imaginal disc and suggest that chromatin accessibility has important implications for Hox target selection and for transcription factor binding in general.
| S-EPMC3071696 | biostudies-literature
Project description:Mutations in the Ultrabithorax (Ubx) gene cause homeotic transformation of the normally two-winged Drosophila into a four-winged mutant fly. Ubx encodes a HOX family transcription factor that specifies segment identity, including transformation of the second set of wings into rudimentary halteres. Ubx is known to control the expression of many genes that regulate tissue growth and patterning, but how it regulates tissue morphogenesis to reshape the wing into a haltere is still unclear. Here, we show that Ubx acts by repressing the expression of two genes in the haltere, Stubble and Notopleural, both of which encode transmembrane proteases that remodel the apical extracellular matrix to promote wing morphogenesis. In addition, Ubx induces expression of the Tissue inhibitor of metalloproteases in the haltere, which prevents the basal extracellular matrix remodelling necessary for wing morphogenesis. Our results provide a long-awaited explanation for how Ubx controls morphogenetic transformation.
| S-EPMC7063672 | biostudies-literature
Project description:Hox genes regionalize the animal body axis by modifying complex morphogenetic and differentiation processes during development. The transformation of wings into halteres by the Hox gene Ultrabithorax (Ubx) in Drosophila melanogaster presents an excellent model system to study the transcriptional networks that control such complex developmental programmes. We have employed an inducible misexpression system to switch on Ubx in the wing epithelium at successive larval, prepupal and pupal stages, and have used microarray expression profiling to identify the primary transcriptional responses to Ubx. We find that Ubx regulates hundreds of downstream genes, mostly in a subtle manner. These targets are largely distinct at the different stages of appendage development and diversification.
2010-12-31 | GSE22354 | GEO
Project description:Hox genes regionalize the animal body axis by modifying complex morphogenetic and differentiation processes during development. The transformation of wings into halteres by the Hox gene Ultrabithorax (Ubx) in Drosophila melanogaster presents an excellent model system to study the transcriptional networks that control such complex developmental programmes. We have employed an inducible misexpression system to switch on Ubx in the wing epithelium at successive larval, prepupal and pupal stages, and have used microarray expression profiling to identify the primary transcriptional responses to Ubx. We find that Ubx regulates hundreds of downstream genes, mostly in a subtle manner. These targets are largely distinct at the different stages of appendage development and diversification. We have generated an experimental fly line combining the nabGal4NP3537-driver, a tub-GAL80ts transgene, and a UAS-UbxIa transgene (the control line was carrying a UAS-eGFP transgene instead). Our core microarray analysis has involved comparison of the transcriptional profile of experimental wings carrying the UAS-UbxIa transgene with that of control wings carrying the UAS-eGFP transgene. Pairwise comparisons have been carried out at three successive developmental stages, in particular at (i) the third instar larval wandering stage, about 4hrs before puparium formation at 29˚C, (ii) the prepupal stage, 6hrs after puparium formation (APF) at 29˚C, and (iii) the early pupal stage, 16hrs APF at 29˚C. Moreover, pairwise comparisons have been carried out with samples developed exclusively at 19˚C (UbxIa or eGFP expression OFF), as well as with samples collected at 16hrs after the temperature shift from 19 to 29˚C (UbxIa or eGFP expression ON). This has allowed us to distinguish the Ubx-dependent effects from the intrinsic expression differences between the fly lines used, and from the temperature-induced responses. We have carried out 4 biological replicates for each condition making a total of 48 hybridizations to Affymetrix Drosophila Genome 2.0 arrays.
2010-12-31 | E-GEOD-22354 | biostudies-arrayexpress