Identification of Hox gene downstream genes at embryonic stages 11 and 12<br></br><br></br>Functional diversification of body parts is dependent on the formation of specialized structures along the various body axes. In animals, region-specific morphogenesis along the anterior-posterior axis is controlled by a group of conserved transcription factors encoded by the Hox genes. Although it has long been assumed that Hox proteins carry out their function by regulating distinct sets of downstream genes, only a small number of such genes have been found, with very few having direct roles in controlling cellular behavior. We have quantitatively identified hundreds of Hox downstream genes in Drosophila by microarray analysis, and validated many of them by in situ hybridizations on loss- and gain-of-function mutants. One important finding is that Hox proteins, despite their similar DNA binding properties in vitro, have highly specific effects on the transcriptome in vivo, as expression of many downstream genes responds primarily to a single Hox protein. In addition, a large fraction of downstream genes encodes realizator functions, which directly affect morphogenetic processes, such as orientation and rate of cell divisions, cell-cell adhesion and communication, cell shape and migration, or cell death. Focusing on these realizators, we provide a framework for the morphogenesis of the maxillary segment. Since the genomic organization of Hox genes and the interaction of Hox proteins with specific cofactors are conserved in vertebrates and invertebrates, and similar classes of downstream genes are regulated by Hox proteins across the metazoan phylogeny, our findings represent a first step towards a mechanistic understanding of morphological diversification within a species as well as between species.
Comparative analysis of Hox downstream genes in Drosophila.
Age, Time
View SamplesAbove ground tissue of 10 day old Arabidopsis seedlings of Col wild-type, 35S-ARR7, arr7, 35S-ARR15 was treated with Cytokinin (benzyladenine), Auxin (indole-3-acetic acid) or both.
Hormonal control of the shoot stem-cell niche.
Age, Specimen part, Treatment
View SamplesResponse to photoperiod in Arabidopsis wildtype, co, and ft mutant plants.
Integration of spatial and temporal information during floral induction in Arabidopsis.
Specimen part
View SamplesInducible overexpression of Arabidopsis meristem regulators by AlcR / AlcA system. Plants harboring 35S::AlcR/AlcA::GOI (GUS control, LEAFY, SHOOTMERSTEMLESS, WUSCHEL)constructs were grown in continous light for 12 days and induced with 1% Ethanol. After 12h of EtOH treatment, seedlings were dissected and RNA was processed from the shoot apex and young leaves. Affymetrix Ath1 arrays were hybridized in duplicates from each experiment.
WUSCHEL controls meristem function by direct regulation of cytokinin-inducible response regulators.
Age, Specimen part, Subject, Compound
View SamplesArabidopsis etiolated seedlings (4d old) Col-0 wild type compared to det3 mutants under various growth conditions
Reduced V-ATPase activity in the trans-Golgi network causes oxylipin-dependent hypocotyl growth Inhibition in Arabidopsis.
Age
View SamplesComparison of Arabidopsis seedlings with disturbed function of CDKB2;1 and CDKB2;2 by either overexpression or knock-down
Requirement of B2-type cyclin-dependent kinases for meristem integrity in Arabidopsis thaliana.
Specimen part
View SamplesGene expression in larval, early third instar eye-antenna discs was assessed to reveal an ATF4 contribution to target gene induction following COX7a knockdown. As hypothesised, these COX7a-RNAi induced target genes require the transcription factor ATF4 for induction, irrespective of concomitant Notch pathway activation through Delta over-expression.
ATF4-Induced Warburg Metabolism Drives Over-Proliferation in Drosophila.
No sample metadata fields
View SamplesGene expression in larval, early third instar eye-antenna discs was assesed in genotypes with Notch Gain-of-Function (UAS-Delta or UAS-Notch[intra2]) over-expression or mitochondrial COX7a Loss-of-function (UAS-COX7a-RNAi) or a combination of both (UAS-Delta, UAS-COX7a-RNAi). The analysis revealed that, despite a strong genetic interaction between Notch pathway activation and knockdown of COX7a, no transcriptional cooperation or synergy was detectable in early L3 eye-antenna discs. Rather, COX7a knockdown induced a unique transcriptional signature, which further experiments revealed to be mediated by the transcription factor ATF4.
ATF4-Induced Warburg Metabolism Drives Over-Proliferation in Drosophila.
No sample metadata fields
View SamplesDynamic regulation of histone methylation by methyltransferases and demethylases plays a central role in regulating the fate of embryonic stem (ES) cells. The histone H3K9 methyltransferase KMT1E, formerly known as ESET or Setdb1, is essential to embryonic development as the ablation of the Setdb1 gene results in peri-implantation lethality and prevents the propagation of ES cells. However, Setdb1- null blastocysts do not display global changes in H3K9 methylation or DNA methylation, arguing against a genome- wide defect. Here we show that conditional deletion of the Setdb1 gene in ES cells results in the upregulation of lineage differentiation markers, especially trophectoderm-specific factors, similar to effects observed upon loss of Oct3/4 expression in ES cells. We demonstrate that KMT1E deficiency in ES cells leads to a decrease in histone H3K9 methylation at and derepression of trophoblast-associated genes such as Cdx2. Furthermore, we find genes that are derepressed upon Setdb1 deletion to overlap with known targets of polycomb mediated repression, suggesting that KMT1E mediated H3K9 methylation acts in concert with polycomb controlled H3K27 methylation. Our studies thus demonstrate an essential role for KMT1E in the control of developmentally regulated gene expression programs in ES cells.
KMT1E mediated H3K9 methylation is required for the maintenance of embryonic stem cells by repressing trophectoderm differentiation.
Specimen part, Treatment
View SamplesHepatitis C Virus (HCV) has a extremely narrow host cell tropism and robustly infects only very few cell lines, most importantly the human hepatoma cell line Huh7. This cell line was isolated from a 57-year old Japanese male with fulminant hepatitis. Different subclones and passages of the Huh7 cell line show up to 1000-fold differences in HCV replication efficiency (permissiveness). In this experiment, we sought to identify factors responsible for these differences by correlating gene expression from eight different uninfected Huh7 variants with their respective HCV permissiveness. HCV replication efficiency was determined using electroporation of a subgenomic luciferase reporter replicon (genotype 1b, "con1/ET") and measuring luciferase activity at 48h post transfection normalized to the input value at 4h p.t.. "Relative permissiveness" of cell lines corresponds to their replication efficiency, normalized to the efficiency in the lowest permissive cells (Huh7 p13 and p28).
Replication vesicles are load- and choke-points in the hepatitis C virus lifecycle.
Specimen part
View Samples