Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Targeted gene expression is a powerful tool for understanding gene function in vivo. In zebrafish, overexpression of gene products is typically accomplished ubiquitously, without temporal and spatial specificity. However, the yeast Gal4/UAS system can be used for targeted gene expression in zebrafish. Here we describe the generation and characterization of Tg[gsc: Gal4-VP16] transgenic zebrafish lines that harbor a construct encoding Gal4-VP16 transcriptional activator under the control of a fragment of the goosecoid gene promoter. Tg[gsc:Gal4-VP16] embryos express Gal4-VP16 RNA in presumptive prechordal plate mesendoderm during late blastula and throughout gastrulation. By crossing these fish to Tg[UAS-GFP] transgenic fish, we show that the gsc:Gal4-VP16 transgene is capable of driving strong expression of a target gene in the prechordal plate and its derivatives during gastrulation and segmentation. Thus, the use of Tg[gsc:Gal4-VP16] fish can help in understanding gene function in the prechordal plate, an embryonic structure that is crucial for normal neural patterning.
Genesis 2006 Dec
PMID:Targeted gene expression in the zebrafish prechordal plate. 1713 14

The first neural crest cells to emigrate from the neural tube are specified as neurons and glial cells and are subsequently followed by melanocytes of the skin. We wished to understand how this fate switch is controlled. The transcriptional repressor FOXD3 is expressed exclusively in the neural/glial precursors and MITF is expressed only in melanoblasts. Moreover, FOXD3 represses melanogenesis. Here we show that avian MITF expression begins very early during melanoblast migration and that loss of MITF in melanoblasts causes them to transdifferentiate to a glial phenotype. Ectopic expression of FOXD3 represses MITF in cultured neural crest cells and in B16-F10 melanoma cells. We also show that FOXD3 does not bind directly to the MITF promoter, but instead interacts with the transcriptional activator PAX3 to prevent the binding of PAX3 to the MITF promoter. Overexpression of PAX3 is sufficient to rescue MITF expression from FOXD3-mediated repression. We conclude that FOXD3 controls the lineage choice between neural/glial and pigment cells by repressing MITF during the early phase of neural crest migration.
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PMID:FOXD3 regulates the lineage switch between neural crest-derived glial cells and pigment cells by repressing MITF through a non-canonical mechanism. 1940 60

Mature oligodendrocytes are critical for myelin maintenance. To understand the molecular basis for this, genetic manipulation of mature oligodendrocytes is needed. Here we generated a mature oligodendrocyte tTA (tetracycline-controlled transcriptional activator) mouse line which, in combination with a tTA-dependent promoter line driving the expression of the desired transgene, can be used for gain-of-function studies. We used an oligodendrocyte promoter, the mouse proteolipid protein (PLP) promoter, to express mammalianized tTA, and generated a PLP-mtTA mouse line. In adults, mtTA mRNA was predominantly detected in brain white matter where it co-localized with PLP mRNA. mtTA-mediated gene induction was confirmed by crossing to mice with a tTA-dependent promoter driving expression of yellow fluorescent protein (tetO-YFP mice). YFP induction in PLP-mtTA::tetO-YFP mice was consistent with PLP expression in adult mature oligodendrocytes and premyelinating-stage myelinating oligodendrocytes. This PLP-mtTA mouse line is the first to enable gain-of-function studies in mature oligodendrocytes with the tet system.
Genesis 2012 May
PMID:Gene induction in mature oligodendrocytes with a PLP-tTA mouse line. 2195 49

Pointed (Pnt) is a transcriptional activator that functions downstream of the highly conserved Receptor Tyrosine Kinase (RTK) signaling pathway. Pnt is an ETS family transcription factor and encodes for two proteins, PntP1 and PntP2. However, while PntP1 is constitutively active, PntP2 is only active after being phosphorylated by MAPK in the RTK pathway. As mutations in pnt perturb the development of several tissues, we wanted to examine the effect and efficacy of using RNAi to target Pnt. We have expressed pnt RNAi in the eyes, oocyte, and heart cells using three different RNAi lines: Valium20, Valium10, and VDRC. Valium20 is distinct since it generates a short hairpin RNA (shRNA), while Valium10 and VDRC produce long hairpin dsRNA. We found that for each tissue examined Valium20 exhibited the strongest phenotype while the Valium10 and VDRC lines produced varying levels of severity and that the long hairpin RNA produced by the Valium10 and VDRC lines are unable to effectively knockdown pnt in embryonic tissues.
Genesis 2017 07
PMID:Short hairpin RNA is more effective than long hairpin RNA in eliciting pointed loss-of-function phenotypes in Drosophila. 2846 29

The ETS family of transcription factors are evolutionarily conserved throughout the metazoan lineage and are critical for regulating cellular processes such as proliferation, differentiation, apoptosis, angiogenesis, and migration. All members have an ETS DNA binding domain, while a subset also has a protein-protein interaction domain called the SAM domain. Pointed (Pnt), an ETS transcriptional activator functions downstream of the receptor tyrosine kinase (RTK) signaling pathway to regulate diverse processes during the development of Drosophila. This review highlights the indispensable role that Pnt plays in regulating normal development and how continued investigation into its function and regulation will provide key mechanistic insight into understanding why the de-regulation of its vertebrate orthologs, ETS1 and ETS2 results in cancer.
Genesis 2018 12
PMID:Lessons from Drosophila Pointed, an ETS family transcription factor and key nuclear effector of the RTK signaling pathway. 3031 58

The generation and maintenance of genome edited zebrafish lines is typically labor intensive due to the lack of an easy visual read-out for the modification. To facilitate this process, we have developed a novel method that relies on the inclusion of an artificial intron with a transgenic marker (InTraM) within the knock-in sequence of interest, which upon splicing produces a transcript with a precise and seamless modification. We have demonstrated this technology by replacing the stop codon of the zebrafish fli1a gene with a transcriptional activator KALTA4, using an InTraM that enables red fluorescent protein expression in the heart.
Genesis 2020 Nov
PMID:Intron with transgenic marker (InTraM) facilitates high-throughput screening of endogenous gene reporter lines. 3278 55