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Ectopic Activation (ectopic + activation)
Selected AbstractsEctopic activation of the transcription promoter for the testis-specific mouse Pgk-2 gene on elimination of a cis -acting upstream DNA regionDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 4 2000Hiroshi Ando Transgenic mice carrying the coding sequence of ,-galactosidase, for which expression was driven by various upstream regions including the transcription promoter of the testis-specific mouse Pgk-2 gene, were generated. Expression of ,-galactosidase mRNA driven by the region between nucleotide positions , 1404 and + 61, with respect to the transcription initiation site numbered + 1, was examined by reverse transcription-mediated polymerase chain reaction, blot hybridization and in situ hybridization, and compared with that of endogenous Pgk-2 mRNA. The results revealed that the 1.4 kb DNA region is sufficient for determining the organ-specific, developmental stage-specific and spermatogenic stage-specific transcription of the mouse Pgk-2 gene. When the region between , 684 and + 61 was used to generate transgenic mice, ,-galactosidase mRNA was detectable not only in the testis, but also in other organs such as brain and lung. However, the timing and cell-type specificity of testicular expression of ,-galactosidase mRNA were retained in these mice. Because the region between , 1404 and , 685 repressed the Pgk-2 promoter in somatic cell-derived cell lines, it is suggested that the organ specificity of Pgk-2 transcription is achieved at least partly by negative regulation. [source] Host and non-host pathogens elicit different jasmonate/ethylene responses in ArabidopsisTHE PLANT JOURNAL, Issue 5 2004Laurent Zimmerli Summary Arabidopsis does not support the growth and asexual reproduction of the barley pathogen, Blumeria graminis f. sp. hordei Bgh). A majority of germlings fail to penetrate the epidermal cell wall and papillae. To gain additional insight into this interaction, we determined whether the salicylic acid (SA) or jasmonate (JA)/ethylene (ET) defence pathways played a role in blocking barley powdery mildew infections. Only the eds1 mutant and NahG transgenics supported a modest increase in penetration success by the barley powdery mildew. We also compared the global gene expression patterns of Arabidopsis inoculated with the non-host barley powdery mildew to those inoculated with a virulent, host powdery mildew, Erysiphe cichoracearum. Genes repressed by inoculations with non-host and host powdery mildews relative to non-inoculated control plants accounted for two-thirds of the differentially expressed genes. A majority of these genes encoded components of photosynthesis and general metabolism. Consistent with this observation, Arabidopsis growth was inhibited following inoculation with Bgh, suggesting a shift in resource allocation from growth to defence. A number of defence-associated genes were induced during both interactions. These genes likely are components of basal defence responses, which do not effectively block host powdery mildew infections. In addition, genes encoding defensins, anti-microbial peptides whose expression is under the control of the JA/ET signalling pathway, were induced exclusively by non-host pathogens. Ectopic activation of JA/ET signalling protected Arabidopsis against two biotrophic host pathogens. Taken together, these data suggest that biotrophic host pathogens must either suppress or fail to elicit the JA/ET signal transduction pathway. [source] Bapx1 homeobox gene gain-of-function mice show preaxial polydactyly and activated Shh signaling in the developing limbDEVELOPMENTAL DYNAMICS, Issue 9 2006Carla Tribioli Abstract To explore Bapx1 homeobox gene function in embryonic control of development, we employed a gain-of-function approach to complement our previous loss-of-function mutant analysis. We show that transgenic mice overexpressing Bapx1 are affected by skeletal defects including hindlimb preaxial polydactyly and tibial hypoplasia. Bapx1 overexpression generates limb anteroposterior patterning defects including induction of Shh signaling and ectopic activation of functions downstream of Shh signaling into the anterior region of the autopod. Moreover, Bapx1 overexpression stimulates formation of limb prechondrogenic condensations. We also show that Shh is reciprocally able to activate Bapx1 expression in mouse embryos as the orthologous hedgehog (hh) does with the bagpipe/Bapx1 gene in Drosophila. Our results indicate that Bapx1 can modulate appendicular skeletal formation, that the genetic hierarchy between Shh/hh and Bapx1/bagpipe has been conserved during evolution, and that in mouse embryos these two genes can influence one another in a genetically reciprocal manner. We conclude that it is reasonable to expect overexpression of Bapx1 in certain forms of polydactyly. Developmental Dynamics 235:2483,2492, 2006. © 2006 Wiley-Liss, Inc. [source] Functional analysis in Drosophila indicates that the NBCCS/PTCH1 mutation G509V results in activation of smoothened through a dominant-negative mechanismDEVELOPMENTAL DYNAMICS, Issue 4 2004Gary R. Hime Abstract Mutations in the human homolog of the patched gene are associated with the developmental (and cancer predisposition) condition Nevoid Basal Cell Carcinoma Syndrome (NBCCS), as well as with sporadic basal cell carcinomas. Most mutations that have been identified in the germline of NBCCS patients are truncating or frameshift mutations, with amino acid substitutions rarely found. We show that a missense mutation in the sterol-sensing domain G509V acts as a dominant negative when assayed in vivo in Drosophila. Ectopic expression of a Drosophila patched transgene, carrying the analogous mutation to G509V, causes ectopic activation of Hedgehog target genes and ectopic membrane stabilisation of Smoothened. The G509V transgene behaves in a manner similar, except in its subcellular distribution, to a C-terminal truncation that has been characterised previously as a dominant-negative protein. G509V exhibits vesicular localisation identical to the wild-type protein, but the C-terminal truncated Patched molecule is localised predominantly to the plasma membrane. This finding suggests that dominant-negative function can be conferred by interruption of different aspects of Patched protein behaviour. Another mutation at the same residue, G509R, did not exhibit dominant-negative activity, suggesting that simple removal of the glycine at 509 is not sufficient to impart dominant-negative function. Developmental Dynamics 229:780,790, 2004. © 2004 Wiley-Liss, Inc. [source] SALL1 truncated protein expression in Townes-Brocks syndrome leads to ectopic expression of downstream genes,,HUMAN MUTATION, Issue 9 2008Susan M. Kiefer Abstract Mutations in SALL1 lead to the dominant multiorgan congenital anomalies that define Townes-Brocks syndrome (TBS). The majority of these mutations result in premature termination codons that would be predicted to trigger nonsense-mediated decay (NMD) of mutant mRNA and cause haploinsufficiency. Our previous studies using a gene targeted mouse model (Sall1- ,Zn) suggested that TBS phenotypes are due to expression of a truncated mutant protein, not haploinsufficiency. In this report, we strengthen this hypothesis by showing that expression of the mutant protein alone in transgenic mice is sufficient to cause limb phenotypes that are characteristic of TBS patients. We prove that the same pathogenetic mechanism elucidated in mice is occurring in humans by demonstrating that truncated SALL1 protein is expressed in cells derived from a TBS patient. TBS mutant protein is capable of dominant negative activity that results in ectopic activation of two downstream genes, Nppa and Shox2, in the developing heart and limb. We propose a model for the pathogenesis of TBS in which truncated Sall1 protein causes derepression of Sall-responsive target genes. Hum Mutat 0,1,8, 2008. Published 2008 Wiley-Liss, Inc. [source] | ||||||||||