her1 and the notch pathway function within the oscillator mechanism that regulates zebrafish somitogenesis

Somite formation is thought to be regulated by an unknown oscillator mechanism that causes the cells of the presomitic mesoderm to activate and then repress the transcription of specific genes in a cyclical fashion. These oscillations create stripes/waves of gene expression that repeatedly pass through the presomitic mesoderm in a posterior-to-anterior direction. In both the mouse and the zebrafish, it has been shown that the notch pathway is required to create the stripes/waves of gene expression. However, it is not clear if the notch pathway comprises part of the oscillator mechanism or if the notch pathway simply coordinates the activity of the oscillator among neighboring cells. In the zebrafish, oscillations in the expression of a hairy-related transcription factor, her1 and the notch ligand deltaC precede somite formation. Our study focuses on how the oscillations in the expression of these two genes is affected in the mutants aei/deltaD and des/notch1, in ‘morpholino knockdowns’ of deltaC and her1 and in double ‘mutant’ combinations. This analysis indicates that these oscillations in gene expression are created by a genetic circuit comprised of the notch pathway and the notch target gene her1. We also show that a later function of the notch pathway can create a segmental pattern even in the absence of prior oscillations in her1 and deltaC expression. Supplementary data available at http://www.eb.tuebingen.mpg.de/papers/holley_dev_2002.html

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Notch Activation Is an Early and Critical Event during T-Cell Leukemogenesis in Ikaros-Deficient Mice

Molecular and Cellular Biology ◽

10.1128/mcb.26.1.209-220.2006 ◽

2006 ◽

Vol 26 (1) ◽

pp. 209-220 ◽

Cited By ~ 116

Author(s):

Alexis Dumortier ◽

Robin Jeannet ◽

Peggy Kirstetter ◽

Eva Kleinmann ◽

MacLean Sellars ◽

...

Keyword(s):

Gene Expression ◽

Tumor Suppressor ◽

Target Gene ◽

Critical Role ◽

Ectopic Expression ◽

Notch Pathway ◽

Notch Target Gene ◽

Target Gene Expression ◽

T Cell Leukemogenesis ◽

Notch Activation

ABSTRACT The Ikaros transcription factor is both a key regulator of lymphocyte differentiation and a tumor suppressor in T lymphocytes. Mice carrying a hypomorphic mutation (IkL/L) in the Ikaros gene all develop thymic lymphomas. IkL/L tumors always exhibit strong activation of the Notch pathway, which is required for tumor cell proliferation in vitro. Notch activation occurs early in tumorigenesis and may precede transformation, as ectopic expression of the Notch targets Hes-1 and Deltex-1 is detected in thymocytes from young IkL/L mice with no overt signs of transformation. Notch activation is further amplified by secondary mutations that lead to C-terminal truncations of Notch 1. Strikingly, restoration of Ikaros activity in tumor cells leads to a rapid and specific downregulation of Notch target gene expression and proliferation arrest. Furthermore, Ikaros binds to the Notch-responsive element in the Hes-1 promoter and represses Notch-dependent transcription from this promoter. Thus, Ikaros-mediated repression of Notch target gene expression may play a critical role in defining the tumor suppressor function of this factor.

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tortuga refines Notch pathway gene expression in the zebrafish presomitic mesoderm at the post-transcriptional level

Developmental Biology ◽

10.1016/j.ydbio.2005.07.032 ◽

2005 ◽

Vol 287 (2) ◽

pp. 225-236 ◽

Cited By ~ 7

Author(s):

Kariena K. Dill ◽

Sharon L. Amacher

Keyword(s):

Gene Expression ◽

Notch Pathway ◽

Transcriptional Level ◽

Presomitic Mesoderm ◽

Pathway Gene

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2049-P: The Chd4 Helicase of the Nucleosome Remodeling and Deacetylase Complex Modulates Pdx1 Target Gene Expression In Vitro

Diabetes ◽

10.2337/db20-2049-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 2049-P

Author(s):

REBECCA K. DAVIDSON ◽

NOLAN CASEY ◽

JASON SPAETH

Keyword(s):

Gene Expression ◽

Target Gene ◽

Nucleosome Remodeling ◽

Target Gene Expression

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Faculty Opinions recommendation of Receptor tyrosine phosphatase psi is required for Delta/Notch signalling and cyclic gene expression in the presomitic mesoderm.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1020702.237451 ◽

2004 ◽

Author(s):

Judith S Eisen

Keyword(s):

Gene Expression ◽

Tyrosine Phosphatase ◽

Notch Signalling ◽

Presomitic Mesoderm ◽

Cyclic Gene ◽

Receptor Tyrosine Phosphatase

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The AML-associated K313 mutation enhances C/EBPα activity by leading to C/EBPα overexpression

Cell Death and Disease ◽

10.1038/s41419-021-03948-6 ◽

2021 ◽

Vol 12 (7) ◽

Author(s):

Ian Edward Gentle ◽

Isabel Moelter ◽

Mohamed Tarek Badr ◽

Konstanze Döhner ◽

Michael Lübbert ◽

...

Keyword(s):

Gene Expression ◽

Cell Culture ◽

Transcription Factor ◽

Transcription Factors ◽

Transcriptional Activity ◽

Target Gene ◽

Wild Type ◽

Elevated Expression ◽

Factor C ◽

Acute Myeloid

AbstractMutations in the transcription factor C/EBPα are found in ~10% of all acute myeloid leukaemia (AML) cases but the contribution of these mutations to leukemogenesis is incompletely understood. We here use a mouse model of granulocyte progenitors expressing conditionally active HoxB8 to assess the cell biological and molecular activity of C/EBPα-mutations associated with human AML. Both N-terminal truncation and C-terminal AML-associated mutations of C/EBPα substantially altered differentiation of progenitors into mature neutrophils in cell culture. Closer analysis of the C/EBPα-K313-duplication showed expansion and prolonged survival of mutant C/EBPα-expressing granulocytes following adoptive transfer into mice. C/EBPα-protein containing the K313-mutation further showed strongly enhanced transcriptional activity compared with the wild-type protein at certain promoters. Analysis of differentially regulated genes in cells overexpressing C/EBPα-K313 indicates a strong correlation with genes regulated by C/EBPα. Analysis of transcription factor enrichment in the differentially regulated genes indicated a strong reliance of SPI1/PU.1, suggesting that despite reduced DNA binding, C/EBPα-K313 is active in regulating target gene expression and acts largely through a network of other transcription factors. Strikingly, the K313 mutation caused strongly elevated expression of C/EBPα-protein, which could also be seen in primary K313 mutated AML blasts, explaining the enhanced C/EBPα activity in K313-expressing cells.

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Comprehensive high-throughput meta-analysis of differentially expressed microRNAs in transcriptomic datasets reveals significant disruption of MAPK/JNK signal transduction pathway in Adult T-cell leukemia/lymphoma

Infectious Agents and Cancer ◽

10.1186/s13027-021-00390-3 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Shahrzad Shadabi ◽

Nargess Delrish ◽

Mehdi Norouzi ◽

Maryam Ehteshami ◽

Fariba Habibian-Sezavar ◽

...

Keyword(s):

Gene Expression ◽

Signal Transduction ◽

T Cell ◽

Network Analysis ◽

High Throughput ◽

Target Gene ◽

Differentially Expressed ◽

Cell Leukemia ◽

Adult T Cell Leukemia ◽

Healthy Donors

Abstract Background Human T-lymphotropic virus 1 (HTLV-1) infection may lead to the development of Adult T-cell leukemia/lymphoma (ATLL). To further elucidate the pathophysiology of this aggressive CD4+ T-cell malignancy, we have performed an integrated systems biology approach to analyze previous transcriptome datasets focusing on differentially expressed miRNAs (DEMs) in peripheral blood of ATLL patients. Methods Datasets GSE28626, GSE31629, GSE11577 were used to identify ATLL-specific DEM signatures. The target genes of each identified miRNA were obtained to construct a protein-protein interactions network using STRING database. The target gene hubs were subjected to further analysis to demonstrate significantly enriched gene ontology terms and signaling pathways. Quantitative reverse transcription Polymerase Chain Reaction (RTqPCR) was performed on major genes in certain pathways identified by network analysis to highlight gene expression alterations. Results High-throughput in silico analysis revealed 9 DEMs hsa-let-7a, hsa-let-7g, hsa-mir-181b, hsa-mir-26b, hsa-mir-30c, hsa-mir-186, hsa-mir-10a, hsa-mir-30b, and hsa-let-7f between ATLL patients and healthy donors. Further analysis revealed the first 5 of DEMs were directly associated with previously identified pathways in the pathogenesis of HTLV-1. Network analysis demonstrated the involvement of target gene hubs in several signaling cascades, mainly in the MAPK pathway. RT-qPCR on human ATLL samples showed significant upregulation of EVI1, MKP1, PTPRR, and JNK gene vs healthy donors in MAPK/JNK pathway. Discussion The results highlighted the functional impact of a subset dysregulated microRNAs in ATLL on cellular gene expression and signal transduction pathways. Further studies are needed to identify novel biomarkers to obtain a comprehensive mapping of deregulated biological pathways in ATLL.

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The EAR Motif in the Arabidopsis MADS Transcription Factor AGAMOUS-Like 15 Is Not Necessary to Promote Somatic Embryogenesis

Plants ◽

10.3390/plants10040758 ◽

2021 ◽

Vol 10 (4) ◽

pp. 758

Author(s):

Sanjay Joshi ◽

Christian Keller ◽

Sharyn E. Perry

Keyword(s):

Gene Expression ◽

Somatic Embryogenesis ◽

Target Gene ◽

Target Genes ◽

Domain Family ◽

Binding Factor ◽

Ear Motif ◽

Carboxyl Terminal ◽

Responsive Element ◽

Carboxy Terminal

AGAMOUS-like 15 (AGL15) is a member of the MADS domain family of transcription factors (TFs) that can directly induce and repress target gene expression, and for which promotion of somatic embryogenesis (SE) is positively correlated with accumulation. An ethylene-responsive element binding factor-associated amphiphilic repression (EAR) motif of form LxLxL within the carboxyl-terminal domain of AGL15 was shown to be involved in repression of gene expression. Here, we examine whether AGL15′s ability to repress gene expression is needed to promote SE. While a form of AGL15 where the LxLxL is changed to AxAxA can still promote SE, another form with a strong transcriptional activator at the carboxy-terminal end, does not promote SE and, in fact, is detrimental to SE development. Select target genes were examined for response to the different forms of AGL15.

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On the way toward regulatable expression systems in acetic acid bacteria: target gene expression and use cases

Applied Microbiology and Biotechnology ◽

10.1007/s00253-021-11269-z ◽

2021 ◽

Author(s):

Philipp Moritz Fricke ◽

Angelika Klemm ◽

Michael Bott ◽

Tino Polen

Keyword(s):

Gene Expression ◽

Acetic Acid ◽

Literature Search ◽

Target Gene ◽

Target Genes ◽

Recombinant Dna ◽

Acetic Acid Bacteria ◽

Homoserine Lactone ◽

Expression Systems ◽

Target Gene Expression

Abstract Acetic acid bacteria (AAB) are valuable biocatalysts for which there is growing interest in understanding their basics including physiology and biochemistry. This is accompanied by growing demands for metabolic engineering of AAB to take advantage of their properties and to improve their biomanufacturing efficiencies. Controlled expression of target genes is key to fundamental and applied microbiological research. In order to get an overview of expression systems and their applications in AAB, we carried out a comprehensive literature search using the Web of Science Core Collection database. The Acetobacteraceae family currently comprises 49 genera. We found overall 6097 publications related to one or more AAB genera since 1973, when the first successful recombinant DNA experiments in Escherichia coli have been published. The use of plasmids in AAB began in 1985 and till today was reported for only nine out of the 49 AAB genera currently described. We found at least five major expression plasmid lineages and a multitude of further expression plasmids, almost all enabling only constitutive target gene expression. Only recently, two regulatable expression systems became available for AAB, an N-acyl homoserine lactone (AHL)-inducible system for Komagataeibacter rhaeticus and an l-arabinose-inducible system for Gluconobacter oxydans. Thus, after 35 years of constitutive target gene expression in AAB, we now have the first regulatable expression systems for AAB in hand and further regulatable expression systems for AAB can be expected. Key points • Literature search revealed developments and usage of expression systems in AAB. • Only recently 2 regulatable plasmid systems became available for only 2 AAB genera. • Further regulatable expression systems for AAB are in sight.

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