gene promoter region
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Retrovirology ◽  
2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Peipei Yuan ◽  
Jun Yan ◽  
Shuang Wang ◽  
Yang Guo ◽  
Xueyan Xi ◽  
...  

Abstract Background Prototype foamy virus (PFV) is nonpathogenic complex retroviruses that express a transcriptional transactivator Tas, which is essential for the activity of viral long terminal repeat (LTR) promoter and internal promoter (IP). Tripartite motif-containing protein 28 (Trim28) is well known as a scaffold protein normally enriched in gene promoter region to repress transcription. We sought to determine if whether Trim28 could be enriched in PFV promoter region to participate the establishment of PFV latency infection. Results In this study, we show that Trim28 restricts Tas-dependent transactivation activity of PFV promoter and negatively regulates PFV replication. Trim28 was found to be enriched in LTR instead of IP promoter regions of PFV genome and contribute to the maintenance of histone H3K9me3 marks on the LTR promoter. Furthermore, Trim28 interacts with Tas and colocalizes with Tas in the nucleus. Besides, we found that Trim28, an E3 ubiquitin ligase, binds directly to and promotes Tas for ubiquitination and degradation. And the RBCC domain of Trim28 is required for the ubiquitination and degradation of Tas. Conclusions Collectively, our findings not only identify a host factor Trim28 negatively inhibits PFV replication by acting as transcriptional restriction factor enriched in viral LTR promoter through modulating H3K9me3 mark here, but also reveal that Trim28 mediated ubiquitin proteasome degradation of Tas as a mechanism underlying Trim28 restricts Tas-dependent transcription activity of PFV promoter and PFV replication. These findings provide new insights into the process of PFV latency establishment. Graphical Abstract


2021 ◽  
Author(s):  
Kanika Jain ◽  
Tyler H. Stanage ◽  
Elizabeth A. Wood ◽  
Michael M. Cox

Deletion of the entire gene encoding the RarA protein of Escherichia coli results in a growth defect and additional deficiencies that were initially ascribed to a lack of RarA function. Further work revealed that most of the effects reflected the presence of sequences in the rarA gene that affect expression of the downstream gene, serS. The serS gene encodes the seryl aminoacyl-tRNA synthetase. Decreases in the expression of serS can trigger the stringent response. The sequences that affect serS expression are located in the last 15 nucleotides of the rarA gene.


Author(s):  
Sandra J. Gutiérrez-Prieto ◽  
Diana M. Torres-López ◽  
Dabeiba A. García-Robayo ◽  
Jorge A. Rey-Cubillos ◽  
Mariluz Gómez-Rodríguez

Abstract Objectives Previous studies showed that noggin gene (NOG) sequence alterations, as well as epigenetic factors, could influence mandibular development. The aim of this study was to analyze clinical characteristics, NOG gene sequences, and promoter methylation sites in patients with mandibular micrognathism. Materials and Methods A total of 35 individuals of five Colombian families were subject to clinical and cephalometric analysis for mandibular micrognathism. One nonaffected individual of each family was included as a control. DNA was isolated from whole blood sample from all individuals by salting out method. Nine NOG gene fragments were amplified by polymerase chain reaction (PCR) and sequenced. Identification of CpG islands for methylation analysis at the NOG gene promoter was performed by MSP-PCR kit (Qiagen R). Statistical Analysis A descriptive statistical analysis was carried out evaluating the presence or absence of genetics variants and the methylation sites in the NOG gene. Results NOG sequence results of affected individuals with mandibular micrognathism for one of the families studied demonstrated that they were heterozygous for 672 C/A (new mutation). For a second family, individuals were heterozygous for 567 G/C (single nucleotide polymorphism [SNP] RS116716909). For DNA analyzed from all patients studied, no methylations were observed at the NOG gene promoter region. Conclusion Our results suggest that 672 C/A and 567 G/C variants could be involved in the presence of mandibular micrognathism. Moreover, lack of methylation sites at the NOG gene promoter region of all individuals studied suggests possibly other epigenetic factors could modulate mandibular growth. The search of genetic variants related with mandibular micrognathism will allow to predict in an integral way the development patterns of the patients and therefore establish a better clinical treatment.


2021 ◽  
Vol 22 (16) ◽  
pp. 8737
Author(s):  
Sabrina Dallavalle ◽  
Salvatore Princiotto ◽  
Luce M. Mattio ◽  
Roberto Artali ◽  
Loana Musso ◽  
...  

DNA repair inhibitors are one of the latest additions to cancer chemotherapy. In general, chemotherapy produces DNA damage but tumoral cells may become resistant if enzymes involved in DNA repair are overexpressed and are able to reverse DNA damage. One of the most successful drugs based on modulating DNA repair are the poly(ADP-ribose) polymerase 1 (PARP1) inhibitors. Several PARP1 inhibitors have been recently developed and approved for clinical treatments. We envisaged that PARP inhibition could be potentiated by simultaneously modulating the expression of PARP 1 and the enzyme activity, by a two-pronged strategy. A noncanonical G-quadruplex-forming sequence within the PARP1 promoter has been recently identified. In this study, we explored the potential binding of clinically approved PARP1 inhibitors to the G-quadruplex structure found at the gene promoter region. The results obtained by NMR, CD, and fluorescence titration confirmed by molecular modeling demonstrated that two out the four PARP1 inhibitors studied are capable of forming defined complexes with the PARP1 G-quadruplex. These results open the possibility of exploring the development of better G-quadruplex binders that, in turn, may also inhibit the enzyme.


Author(s):  
Si-Qiang Zheng ◽  
Huan-Xin Chen ◽  
Xiao-Cheng Liu ◽  
Qin Yang ◽  
Guo-Wei He

Ventricular septal defects (VSD) are the most common congenital heart defects (CHD). Studies have documented that ISL1 has a crucial impact on cardiac growth, but the role of variants in the ISL1 gene promoter in patients with VSD has not been explored. In 400 subjects (200 isolated and sporadic VSD patients: 200 healthy controls), we investigated the ISL1 gene promoter variant and performed cellular functional experiments by using the dual-luciferase reporter assay to verify the impact on gene expression. In the ISL1 promoter, 5 variants were found only in VSD patients by sequencing. Cellular functional experiments demonstrated that three variants decreased the transcriptional activity of the ISL1 promoter (P < 0.05). Further analysis with the online JASPAR database demonstrated that a cluster of putative binding sites for transcription factors may be altered by these variants, possibly resulting in change of ISL1 protein expression and VSD formation. Our study has for the first time identified novel variants in the ISL1 gene promoter region in the Han Chinese patients with isolated and sporadic VSD. Additionally, the cellular functional experiments, electrophoretic mobility shift assay, and bioinformatic analysis have demonstrated that these variants significantly alter the expression of the ISL1 gene and affect the binding of transcription factors, likely resulting in VSD. Therefore, this study may provide new insights into the role of the gene promoter region for a better understanding of genetic basis of the formation of CHD and may promote further investigations on mechanism of the formation of CHD.


2021 ◽  
Author(s):  
Plinio Trabasso ◽  
Tetsuhiro Matsuzawa ◽  
Teppei Arai ◽  
Daisuke Hagiwara ◽  
Yuzuru Mikami ◽  
...  

Infections due to triazole-resistant Aspergillus fumigatus are increasingly reported worldwide and are associated with treatment failure and mortality. The principal class of azole-resistant isolates is characterized by the presence of tandem repeats of 34 bp or 46 bp (TR34 or TR46) within the promoter region of the cyp51A gene. Loop-mediated isothermal amplification (LAMP) is a widely >used nucleic acid amplification system with high rapidity and specificity. In this paper, we report a new LAMP assay method to detect the 46 bp tandem repeat insertion in the cyp51A gene promoter region named TR46-LAMP assay, based on the use of newly designed specific LAMP primer sets. TR46 is a high-prevalence allele that is associated with the occurrence of multi-triazole resistance of A. fumigatus in patients as well as isolates from the environment. This newly designed TR46-LAMP assay was validated as a useful method for specific detection of azole-resistant A. fumigatus isolates bearing TR462 as well as TR463 in the cyp51A gene promoter region. It could also differentiate azole-resistant isolates of TR46 tandem repeats from those with TR34 tandem repeats in cyp51A genes. These results showed this TR46-LAMP method is specific, rapid, and also provides crucial insights to enable the development of novel antifungal therapeutic strategies against severe fungal infections due to A. fumigatus with TR46 tandem repeats.


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