scholarly journals Characterization of the human TARDBP gene promoter

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marco Baralle ◽  
Maurizio Romano
Keyword(s):  
Gene Promoter ◽  
Transcriptional Level ◽  
Developmentally Regulated ◽  
Cis Acting ◽  
Transcript Stability ◽  
Intron 1 ◽  
Main Component ◽  
Als Patients

AbstractThe expression of TDP-43, the main component of neuronal intracellular inclusions across a broad spectrum of ALS and FTD disorders, is developmentally regulated and studies in vivo have shown that TDP-43 overexpression can be toxic, even before observation of pathological aggregates. Starting from these observations, the regulation of its expression at transcriptional level might represent a further key element for the pathogenesis of neurodegenerative diseases. Therefore, we have characterized the human TARDBP promoter, in order to study the transcriptional mechanisms of expression. Mapping of cis-acting elements by luciferase assays in different cell outlined that the activity of the promoter seems to be higher in SH-SY5Y, Neuro2A, and HeLa than in HEK293. In addition, we tested effects of two SNPs found in the promoter region of ALS patients and observed no significant effect on transcription levels in all tested cell lines. Lastly, while TDP-43 overexpression did not affect significantly the activity of its promoter (suggesting that TDP-43 does not influence its own transcription), the presence of the 5′UTR sequence and of intron-1 splicing seem to impact positively on TDP-43 expression without affecting transcript stability. In conclusion, we have identified the region spanning nucleotides 451–230 upstream from the transcription start site as the minimal region with a significant transcription activity. These results lay an important foundation for exploring the regulation of the TARDBP gene transcription by exogenous and endogenous stimuli and the implication of transcriptional mechanisms in the pathogenesis of TDP-43 proteinopathies.

Characterization of the Human TARDBP Gene Promoter

2020 ◽  
Author(s):  
Marco Baralle ◽  
Maurizio Romano
Keyword(s):  
Gene Promoter ◽  
Transcriptional Level ◽  
Developmentally Regulated ◽  
Cis Acting ◽  
Intron 1 ◽  
Main Component ◽  
Als Patients ◽  
Minimal Region

Abstract The expression of TDP-43, the main component of neuronal intracellular inclusions across a broad spectrum of ALS and FTD disorders, is developmentally regulated and studies in vivo have shown that TDP-43 overexpression can be toxic, even before observation of pathological aggregates. Starting from these observations, the regulation of its expression at transcriptional level might represent a further key element for the pathogenesis of neurodegenerative diseases. Therefore, we have characterized the human TARDBP promoter, in order to study the transcriptional mechanisms of expression. Mapping of cis-acting elements by luciferase assays in different cells outlined that the activity of the promoter seems to be higher in cell lines of neuronal origin. We have identified the first 400 nucleotides upstream from the transcription start site as the minimal region with a significant transcription activity. In addition, we tested the effects of two SNPs found in the the promoter region of ALS patients and observed no significant effect on transcription levels. Then, TDP-43 overexpression did not affect significantly the activity of its promoter, suggesting that TDP-43 does not influence its own transcription. Finally, the presence of the 5'UTR sequence and of intron-1 splicing seem to impact positively on TDP-43 expression at transcriptional level.

scholarly journals Characterization of cis-acting elements in the rat ATP citrate-lyase gene promoter

2002 ◽  
Vol 34 (1) ◽  
pp. 60-68 ◽  
Author(s):  
Young-An Moon ◽  
Sahng-Wook Park ◽  
Kyung-Sup Kim
Keyword(s):  
Gene Promoter ◽  
Atp Citrate Lyase ◽  
Cis Acting ◽  
Citrate Lyase

scholarly journals Identification and characterization of cis-acting elements conferring insulin responsiveness on hamster cholesterol 7α-hydroxylase gene promoter

2000 ◽  
Vol 347 (1) ◽  
pp. 147 ◽  
Author(s):  
Emma DE FABIANI ◽  
Maurizio CRESTANI ◽  
Maria MARRAPODI ◽  
Alessandra PINELLI ◽  
Viviana GOLFIERI ◽  
...  
Keyword(s):  
Gene Promoter ◽  
Cis Acting ◽  
Hydroxylase Gene ◽  
Insulin Responsiveness ◽  
Identification And Characterization

The NFY Transcription Factor Mediates Induction of the von Willebrand Factor Promoter by Irradiation

2001 ◽  
Vol 85 (05) ◽  
pp. 837-844 ◽  
Author(s):  
Angela Bertagna ◽  
Nadia Jahroudi
Keyword(s):  
Transcription Factor ◽  
Von Willebrand Factor ◽  
Thrombus Formation ◽  
Core Promoter ◽  
Transcriptional Level ◽  
Cis Acting ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Secretion

SummaryIonizing irradiation in patients is proposed to cause thrombus formation. An increase in von Willebrand factor secretion in response to irradiation is a major contributing factor to thrombus formation. We have previously reported that the increased VWF secretion in response to irradiation is mediated at the transcriptional level. The VWF core promoter fragment (sequences –90 to +22) was shown to contain the necessary cis-acting element(s) to mediate the irradiation response of the VWF gene. Here we report that a CCAAT element in the VWF promoter is the cis-acting element necessary for irradiation induction and that the NFY transcription factor interacts with this element. These analyses demonstrate that inhibition of NFY’s interaction with the CCAAT element abolishes the irradiation induction of the VWF promoter. These results provide a novel role for NFY and add this factor to the small list of irradiation-responsive transcription factors. Coimmunoprecipitation experiments demonstrated that NFY is associated with the histone acetylase P/CAF in vivo and that irradiation resulted in an increased association of NFY with coactivator P/CAF. We propose that irradiation induction of the VWF promoter involves a mechanism resulting in increased recruitment of the coactivator P/CAF to the promoter via the NFY transcription factor.

scholarly journals Characterization of an amphioxus heat-shock protein gene promoter and its application in vivo

2017 ◽  
Vol 61 (10-11-12) ◽  
pp. 785-792 ◽  
Author(s):  
Chaofan Xing ◽  
Guang Li ◽  
Xian Liu ◽  
Xi Deng ◽  
Yiquan Wang
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Protein Gene ◽  
Gene Promoter ◽  
Heat Shock Protein Gene

scholarly journals SIRT1 Promotes Cell Survival under Stress by Deacetylation-Dependent Deactivation of Poly(ADP-Ribose) Polymerase 1

2009 ◽  
Vol 29 (15) ◽  
pp. 4116-4129 ◽  
Author(s):  
Senthilkumar B. Rajamohan ◽  
Vinodkumar B. Pillai ◽  
Madhu Gupta ◽  
Nagalingam R. Sundaresan ◽  
Konstantin G. Birukov ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Cell Survival ◽  
Cross Talk ◽  
Gene Promoter ◽  
Stress Conditions ◽  
Transcriptional Level ◽  
A Cell

ABSTRACT Poly(ADP-ribose) polymerase 1 (PARP1) and SIRT1 deacetylase are two NAD-dependent enzymes which play major roles in the decision of a cell to live or to die in a stress situation. Because of the dependence of both enzymes on NAD, cross talk between them has been suggested. Here, we show that PARP1 is acetylated after stress of cardiomyocytes, resulting in the activation of PARP1, which is independent of DNA damage. SIRT1 physically binds to and deacetylates PARP1. Increased acetylation of PARP1 was also detected in hearts of SIRT1−/− mice, compared to that detected in the hearts of SIRT1+/+ mice, confirming a role of SIRT1 in regulating the PARP1 acetylation in vivo. SIRT1-dependent deacetylation blocks PARP1 activity, and it protects cells from PARP1-mediated cell death. We also show that SIRT1 negatively regulates the activity of the PARP1 gene promoter, thus suggesting that the deacetylase controls the PARP1 activity at the transcriptional level as well. These data demonstrate that the activity of PARP1 is under the control of SIRT1, which is necessary for survival of cells under stress conditions.

scholarly journals Characterization of the p150,95 leukocyte integrin alpha subunit (CD11c) gene promoter. Identification of cis-acting elements.

1993 ◽  
Vol 268 (2) ◽  
pp. 1187-1193
Author(s):  
M. López-Cabrera ◽  
A. Nueda ◽  
A. Vara ◽  
J. García-Aguilar ◽  
A. Tugores ◽  
...  
Keyword(s):  
Gene Promoter ◽  
Alpha Subunit ◽  
Cis Acting

scholarly journals Characterization of C9orf72 haplotypes to evaluate the effects of normal and pathological variations on its expression and splicing

PLoS Genetics ◽  
2021 ◽  
Vol 17 (3) ◽  
pp. e1009445
Author(s):  
Israel Ben-Dor ◽  
Crystal Pacut ◽  
Yuval Nevo ◽  
Eva L. Feldman ◽  
Benjamin E. Reubinoff
Keyword(s):  
Single Nucleotide ◽  
Hexanucleotide Repeat ◽  
Intron 1 ◽  
Specific Analysis ◽  
Expanded Allele ◽  
Allele Specific ◽  
Als Patients ◽  
Intron 2 ◽  
Lateral Sclerosis

Expansion of the hexanucleotide repeat (HR) in the first intron of the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in Caucasians. All C9orf72-ALS/FTD patients share a common risk (R) haplotype. To study C9orf72 expression and splicing from the mutant R allele compared to the complementary normal allele in ALS/FTD patients, we initially created a detailed molecular map of the single nucleotide polymorphism (SNP) signature and the HR length of the various C9orf72 haplotypes in Caucasians. We leveraged this map to determine the allelic origin of transcripts per patient, and decipher the effects of pathological and normal HR lengths on C9orf72 expression and splicing. In C9orf72 ALS patients’ cells, the HR expanded allele, compared to non-R allele, was associated with decreased levels of a downstream initiated transcript variant and increased levels of transcripts initiated upstream of the HR. HR expanded R alleles correlated with high levels of unspliced intron 1 and activation of cryptic donor splice sites along intron 1. Retention of intron 1 was associated with sequential intron 2 retention. The SNP signature of C9orf72 haplotypes described here enables allele-specific analysis of transcriptional products and may pave the way to allele-specific therapeutic strategies.

scholarly journals Identification and Characterization of SpcU, a Chaperone Required for Efficient Secretion of the ExoU Cytotoxin

1998 ◽  
Vol 180 (23) ◽  
pp. 6224-6231 ◽  
Author(s):  
Viviane Finck-Barbançon ◽  
Timothy L. Yahr ◽  
Dara W. Frank
Keyword(s):  
Amino Acids ◽  
Noncovalent Complex ◽  
Open Reading Frames ◽  
Transcriptional Level ◽  
Exoenzyme S ◽  
Coding Regions ◽  
Acute Cytotoxicity

ABSTRACT In recent studies, we have shown that Pseudomonas aeruginosa strains that are acutely cytotoxic in vitro damage the lung epithelium in vivo. Genetic analysis indicated that the factor responsible for acute cytotoxicity was controlled by ExsA and therefore was part of the exoenzyme S regulon. The specific virulence determinant responsible for epithelial damage in vivo and cytotoxicity in vitro was subsequently mapped to the exoU locus. The present studies are focused on a genetic characterization of the exoUlocus. Northern blot analyses and complementation experiments indicated that a region downstream of exoU was expressed and that the expression of this region corresponded to increased ExoU secretion. DNA sequence analysis of a region downstream of exoU identified several potential coding regions. One of these open reading frames, SpcU (specific Pseudomonas chaperone for ExoU), encoded a small 15-kDa acidic protein (137 amino acids [pI 4.4]) that possessed a leucine-rich motif associated with the Syc family of cytosolic chaperones for the Yersinia Yops. T7 expression analysis and nickel chromatography of histidine-tagged proteins indicated that ExoU and SpcU associated as a noncovalent complex when coexpressed inEscherichia coli. The association of ExoU and SpcU required amino acids 3 to 123 of ExoU. In P. aeruginosa, ExoU and SpcU are coordinately expressed as an operon that is controlled at the transcriptional level by ExsA.

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