scholarly journals Protein Delivery of an Artificial Transcription Factor Restores Widespread Ube3a Expression in an Angelman Syndrome Mouse Brain

2016 ◽  
Vol 24 (3) ◽  
pp. 548-555 ◽  
Author(s):  
Barbara J Bailus ◽  
Benjamin Pyles ◽  
Michelle M McAlister ◽  
Henriette O'Geen ◽  
Sarah H Lockwood ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mouse Brain ◽  
Angelman Syndrome ◽  
Protein Delivery ◽  
Artificial Transcription Factor

scholarly journals 26. Protein Delivery of an Artificial Transcription Factor Restores Widespread Ube3a Expression in an Angelman Syndrome Mouse Brain

2016 ◽  
Vol 24 ◽  
pp. S12 ◽  
Author(s):  
Barbara Bailus ◽  
Benjamin Pyles ◽  
Michelle McAlister ◽  
Henriette O'Geen ◽  
Sarah Lockwood ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mouse Brain ◽  
Angelman Syndrome ◽  
Protein Delivery ◽  
Artificial Transcription Factor

scholarly journals Creation of a Six-fingered Artificial Transcription Factor That Represses the Hepatitis B Virus HBx Gene Integrated into a Human Hepatocellular Carcinoma Cell Line

2012 ◽  
Vol 18 (4) ◽  
pp. 378-387 ◽  
Author(s):  
Xinghui Zhao ◽  
Zhanzhong Zhao ◽  
Junwei Guo ◽  
Peitang Huang ◽  
Xudong Zhu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcription Factor ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Cell Line ◽  
Hbv Infection ◽  
Luciferase Reporter ◽  
Artificial Transcription Factor ◽  
Chronic Hepatitis B Virus ◽  
B Virus

Chronic hepatitis B virus (HBV) infection is an independent risk factor for the development of hepatocellular carcinoma (HCC). The HBV HBx gene is frequently identified as an integrant in the chromosomal DNA of patients with HCC. HBx encodes the X protein (HBx), a putative viral oncoprotein that affects transcriptional regulation of several cellular genes. Therefore, HBx may be an ideal target to impede the progression of HBV infection–related HCC. In this study, integrated HBx was transcriptionally downregulated using an artificial transcription factor (ATF). Two three-fingered Cys2-His2 zinc finger (ZF) motifs that specifically recognized two 9-bp DNA sequences regulating HBx expression were identified from a phage-display library. The ZF domains were linked into a six-fingered protein that specified an 18-bp DNA target in the Enhancer I region upstream of HBx. This DNA-binding domain was fused with a Krüppel-associated box (KRAB) transcriptional repression domain to produce an ATF designed to downregulate HBx integrated into the Hep3B HCC cell line. The ATF significantly repressed HBx in a luciferase reporter assay. Stably expressing the ATF in Hep3B cells resulted in significant growth arrest, whereas stably expressing the ATF in an HCC cell line lacking integrated HBx (HepG2) had virtually no effect. The targeted downregulation of integrated HBx is a promising novel approach to inhibiting the progression of HBV infection–related HCC.

Myf5 is a novel early axonal marker in the mouse brain and is subjected to post-transcriptional regulation in neurons

Development ◽  
2000 ◽  
Vol 127 (2) ◽  
pp. 319-331 ◽  
Author(s):  
P. Daubas ◽  
S. Tajbakhsh ◽  
J. Hadchouel ◽  
M. Primig ◽  
M. Buckingham
Keyword(s):  
Transcription Factor ◽  
Mouse Brain ◽  
Mrna Translation ◽  
Adult Brain ◽  
Protein Accumulation ◽  
Embryonic Mouse ◽  
Signalling Molecules ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
The Brain

Myf5 is a key basic Helix-Loop-Helix transcription factor capable of converting many non-muscle cells into muscle. Together with MyoD it is essential for initiating the skeletal muscle programme in the embryo. We previously identified unexpected restricted domains of Myf5 transcription in the embryonic mouse brain, first revealed by Myf5-nlacZ(+/)(−) embryos (Tajbakhsh, S. and Buckingham, M. (1995) Development 121, 4077–4083). We have now further characterized these Myf5 expressing neurons. Retrograde labeling with diI, and the use of a transgenic mouse line expressing lacZ under the control of Myf5 regulatory sequences, show that Myf5 transcription provides a novel axonal marker of the medial longitudinal fasciculus (mlf) and the mammillotegmental tract (mtt), the earliest longitudinal tracts to be established in the embryonic mouse brain. Tracts projecting caudally from the developing olfactory system are also labelled. nlacZ and lacZ expression persist in the adult brain, in a few ventral domains such as the mammillary bodies of the hypothalamus and the interpeduncular nucleus, potentially derived from the embryonic structures where the Myf5 gene is transcribed. To investigate the role of Myf5 in the brain, we monitored Myf5 protein accumulation by immunofluorescence and immunoblotting in neurons transcribing the gene. Although Myf5 was detected in muscle myotomal cells, it was absent in neurons. This would account for the lack of myogenic conversion in brain structures and the absence of a neural phenotype in homozygous null mutants. RT-PCR experiments show that the splicing of Myf5 primary transcripts occurs correctly in neurons, suggesting that the lack of Myf5 protein accumulation is due to regulation at the level of mRNA translation or protein stability. In the embryonic neuroepithelium, Myf5 is transcribed in differentiated neurons after the expression of neural basic Helix-Loop-Helix transcription factors. The signalling molecules Wnt1 and Sonic hedgehog, implicated in the activation of Myf5 in myogenic progenitor cells in the somite, are also produced in the viscinity of the Myf5 expression domain in the mesencephalon. We show that cells expressing Wnt1 can activate neuronal Myf5-nlacZ gene expression in dissected head explants isolated from E9.5 embryos. Furthermore, the gene encoding the basic Helix-Loop-Helix transcription factor mSim1 is expressed in adjacent cells in both the somite and the brain, suggesting that signalling molecules necessary for the activation of mSim1 as well as Myf5 are present at these different sites in the embryo. This phenomenon may be widespread and it remains to be seen how many other potentially potent regulatory genes, in addition to Myf5, when activated do not accumulate protein at inappropriate sites in the embryo.

scholarly journals Bacterium-Enabled Transient Gene Activation by Artificial Transcription Factor for Resolving Gene Regulation in Maize

2021 ◽  
Author(s):  
Mingxia Zhao ◽  
Zhao Peng ◽  
Yang Qin ◽  
Ling Zhang ◽  
Bin Tian ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Protein Delivery ◽  
Graphical Model ◽  
Gene Activation ◽  
Cuticular Wax ◽  
Host Cells ◽  
Myb Transcription Factor ◽  
Leaf Phenotype

ABSTRACTCellular functions are diversified through intricate transcription regulations, and an understanding gene regulation networks is essential to elucidating many developmental processes and environmental responses. Here, we employed the Transcriptional-Activator Like effectors (TALes), which represent a family of transcription factors that are synthesized by members of the γ-proteobacterium genus Xanthomonas and secreted to host cells for activation of targeted host genes. Through delivery by the maize pathogen, Xanthomonas vasicola pv. vasculorum, designer TALes (dTALes), which are synthetic TALes, were used to induce the expression of the maize gene glossy3 (gl3), a MYB transcription factor gene involved in the cuticular wax biosynthesis. RNA-Seq analysis of leaf samples identified 146 gl3 downstream genes. Eight of the nine known genes known to be involved in the cuticular wax biosynthesis were up-regulated by at least one dTALe. A top-down Gaussian graphical model predicted that 68 gl3 downstream genes were directly regulated by GL3. A chemically induced mutant of the gene Zm00001d017418 from the gl3 downstream gene, encoding aldehyde dehydrogenase, exhibited a typical glossy leaf phenotype and reduced epicuticular waxes. The bacterial protein delivery of artificial transcription factors, dTALes, proved to be a straightforward and powerful approach for the revelation of gene regulation in plants.

scholarly journals Long term environmental tobacco smoke activates nuclear transcription factor-kappa B, activator protein-1, and stress responsive kinases in mouse brain

2006 ◽  
Vol 71 (11) ◽  
pp. 1602-1609 ◽  
Author(s):  
Sunil K. Manna ◽  
Thirumalai Rangasamy ◽  
Kimberly Wise ◽  
Shubhashish Sarkar ◽  
Shishir Shishodia ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mouse Brain ◽  
Environmental Tobacco Smoke ◽  
Tobacco Smoke ◽  
Activator Protein 1 ◽  
Nuclear Transcription Factor ◽  
Activator Protein

scholarly journals Purified Protein Delivery to Activate an Epigenetically Silenced Allele in Mouse Brain

2018 ◽  
pp. 227-239 ◽  
Author(s):  
Benjamin Pyles ◽  
Barbara J. Bailus ◽  
Henriette O’Geen ◽  
David J. Segal
Keyword(s):  
Mouse Brain ◽  
Protein Delivery

ACTIVATION OF NUCLEAR TRANSCRIPTION FACTOR–κB IN MOUSE BRAIN INDUCED BY A SIMULATED MICROGRAVITY ENVIRONMENT

2005 ◽  
Vol 41 (3) ◽  
pp. 118 ◽  
Author(s):  
KIMBERLY C. WISE ◽  
SUNIL K. MANNA ◽  
KEIKO YAMAUCHI ◽  
VANI RAMESH ◽  
BOBBY L. WILSON ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mouse Brain ◽  
Simulated Microgravity ◽  
Microgravity Environment ◽  
Nuclear Transcription Factor

scholarly journals Utrophin Up-Regulation by an Artificial Transcription Factor in Transgenic Mice

PLoS ONE ◽  
2007 ◽  
Vol 2 (8) ◽  
pp. e774 ◽  
Author(s):  
Elisabetta Mattei ◽  
Nicoletta Corbi ◽  
Maria Grazia Di Certo ◽  
Georgios Strimpakos ◽  
Cinzia Severini ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transgenic Mice ◽  
Artificial Transcription Factor

Cell type-specific and sexually dimorphic expression of transcription factor AP-2 in the adult mouse brain

Neuroscience ◽  
2005 ◽  
Vol 134 (3) ◽  
pp. 907-919 ◽  
Author(s):  
D.J. Coelho ◽  
D.J. Sims ◽  
P.J. Ruegg ◽  
I. Minn ◽  
A.R. Muench ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mouse Brain ◽  
Adult Mouse ◽  
Sexually Dimorphic ◽  
Cell Type ◽  
Adult Mouse Brain ◽  
Sexually Dimorphic Expression ◽  
Cell Type Specific ◽  
Dimorphic Expression
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