Mode of Binding of the Fur Protein to Target DNA: Negative Regulation of Iron-Controlled Gene Expression

2014 ◽  
pp. 185-196 ◽  
Author(s):  
Víctor de Lorenzo ◽  
José Perez-Martín ◽  
Lucía Escolar ◽  
Graziano Pesole ◽  
Giovanni Bertoni
2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jiao Fan ◽  
Yige Ding ◽  
Chao Ren ◽  
Ziguo Song ◽  
Jie Yuan ◽  
...  

AbstractCytosine or adenine base editors (CBEs or ABEs) hold great promise in therapeutic applications because they enable the precise conversion of targeted base changes without generating of double-strand breaks. However, both CBEs and ABEs induce substantial off-target DNA editing, and extensive off-target RNA single nucleotide variations in transfected cells. Therefore, the potential effects of deaminases induced by DNA base editors are of great importance for their clinical applicability. Here, the transcriptome-wide deaminase effects on gene expression and splicing is examined. Differentially expressed genes (DEGs) and differential alternative splicing (DAS) events, induced by base editors, are identified. Both CBEs and ABEs generated thousands of DEGs and hundreds of DAS events. For engineered CBEs or ABEs, base editor-induced variants had little effect on the elimination of DEGs and DAS events. Interestingly, more DEGs and DAS events are observed as a result of over expressions of cytosine and adenine deaminases. This study reveals a previously overlooked aspect of deaminase effects in transcriptome-wide gene expression and splicing, and underscores the need to fully characterize such effects of deaminase enzymes in base editor platforms.


2007 ◽  
Vol 189 (7) ◽  
pp. 2629-2636 ◽  
Author(s):  
Hyun-Jung Lee ◽  
So Hyun Bang ◽  
Kyu-Ho Lee ◽  
Soon-Jung Park

ABSTRACT In pathogenic bacteria, the ability to acquire iron, which is mainly regulated by the ferric uptake regulator (Fur), is essential to maintain growth as well as its virulence. In Vibrio vulnificus, a human pathogen causing gastroenteritis and septicemia, fur gene expression is positively regulated by Fur when the iron concentration is limited (H.-J. Lee et al., J. Bacteriol. 185:5891-5896, 2003). Footprinting analysis revealed that an upstream region of the fur gene was protected by the Fur protein from DNase I under iron-depleted conditions. The protected region, from −142 to −106 relative to the transcription start site of the fur gene, contains distinct AT-rich repeats. Mutagenesis of this repeated sequence resulted in abolishment of binding by Fur. To confirm the role of this cis-acting element in Fur-mediated control of its own gene in vivo, fur expression was monitored in V. vulnificus strains using a transcriptional fusion containing the mutagenized Fur-binding site (fur mt::luxAB). Expression of fur mt::luxAB showed that it was not regulated by Fur and was not influenced by iron concentration. Therefore, this study demonstrates that V. vulnificus Fur acts as a positive regulator under iron-limited conditions by direct interaction with the fur upstream region.


2021 ◽  
Author(s):  
Khyber Shinwari ◽  
Guojun Liu ◽  
Mikhail Bolkov ◽  
Monib Ullah ◽  
Irina Tuzankina

HOIL-1/RBCK1 deficiency is a new autosomal receiving disorder with dysfunctional cellular responses to pro-inflammatory cytokines, leading to auto-inflammation, pyogenic bacterial disease, and muscle amylopectinosis growth. Our study with integrated bioinformatics studies of the feature genes and the correlative gene functions, investigated the molecular mechanisms of RBCK1 deficiency. GSE31064 dataset expression profile was downloaded from the Omnibus Gene Expression database. Between RBCK1, MYDK88, NEMO deficient fibroblast, and healthy fibroblast specimens, differentially expressed genes (DEGs) were defined. Gene ontology (GO) gene role enrichment analysis and the Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were performed using the Annotation, Visualization and Integrated Discovery Database (DAVID). The protein-protein interaction (PPI) of these DEGs was visualized using Cytoscape. GO analysis revealed that the “Skeletal system development, Extracellular matrix organization, Positive regulation of cell migration, Negative regulation of canonical Wnt signaling pathway, Cell adhesion, Angiogenesis and Negative regulation of BMP signaling pathway, Serine-type carboxypeptidase activity, Polysaccharide binding, Calcium ion binding, frizzled binding, Neuropilin binding, and cell adhesion molecule binding, extracellular exosome, extracellular space, extracellular region, lysosomal lumen, endoplasmic reticulum lumen, cell surface and focal adhesion to BP, MF, and CC, respectively. The study of the KEGG pathway showed that the complement and coagulation cascade, interactions of the ECM receptor, PI3K-Akt signaling pathway, PPAR signaling pathway, TGF-beta signaling pathway, cancer pathway, viral carcinogenesis and focal adhesion pathway were closely correlated with the incidence of RBCK1 deficiency. Importantly, it has been predicted that TK1, AURKB, CDCA2, UBE2C, KIFC1, CEP55, CDCA3, GINS2, MCM6 and CDC45 are significantly associated with RCBK1 deficiency. Our study offers a record of damaged genes and pathways in RCBK1, which will boost the understanding of RBCK1 deficiency pathogenesis and other inherent immunodeficiency diseases. This research has the potential and can possibly use in the clinic for diagnosis and targeted therapy of HOIL-1/RBCK1 disorder and other inherent immunodeficiencies.


Biochimie ◽  
1991 ◽  
Vol 73 (1) ◽  
pp. 41-45 ◽  
Author(s):  
M. Raymondjean ◽  
S. Voulont ◽  
M. Cognet ◽  
J.F. Decaux ◽  
N. Puzenat ◽  
...  

2019 ◽  
Vol 71 (6) ◽  
pp. 1792-1800
Author(s):  
K Nagaki ◽  
N Yamaji

Abstract Information about the positioning of individual loci in the nucleus and the status of epigenetic modifications at these loci in each cell contained in plant tissue increases our understanding of how cells in a tissue coordinate gene expression. To obtain such information, a less damaging method of visualizing DNA in tissue that can be used with immunohistochemistry is required. Recently, a less damaging DNA visualization method using the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/associated caspase 9) system, named RNA-guided endonuclease–in situ labeling (RGEN-ISL), was reported. This system made it possible to visualize a target DNA locus in a nucleus fixed on a glass slide with a set of simple operations, but it could not be applied to cells in plant tissues. In this work, we have developed a modified RGEN-ISL method with decrosslinking that made it possible to simultaneously detect the DNA loci and immunohistochemistry signals, including histone modification, in various types of plant tissues and species.


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