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Nanoinformatics: An Emerging Trend in Cancer Therapeutics
Published in Rajesh Singh Tomar, Anurag Jyoti, Shuchi Kaushik, Nanobiotechnology, 2020
Medha Pandya, Snehal Jani, Vishakha Dave, Rakesh Rawal
In this section, the author discusses their work on synthetic ssDNA as a drug for OFP. The functional analysis revealed that AF9-MLL OFP possesses the CXXC domain: CpG DNA binding domain. The protein-DNA interactions are the foundation of gene expression and DNA modification. These interactions are the prerequisite for the differentiating structural models. As only a few numbers of structures for protein-DNA complexes determined by experimental methods, computation methods postulate a promising way to fulfill the need. The vertebrate DNA is able to chemically alter by methylation of the five locations of the cytosine base in the context of CpG (5’-Cytosine-phosphate-Guanine-3’) dinucleotides. This alteration generates a binding site for the methyl-CpG-binding domain (MBD) proteins that direct the chromatin-modifying actions that considered contributing to transcriptional repression and control heterochromatic regions of the genome. In contrast with DNA methylation that found broadly across vertebrate genomes, non-methylated DNA is concentrated in regions known as CGIs (CpG islands). Recently, families of proteins which encode a ZF-CXXC (zinc finger-CXXC) domain have been determined to specifically distinguish non-methylated DNA and recruit chromatin-modifying activities to CGI elements [37].
Genetic and Epigenetic Considerations in iPSC Technology
Published in Deepak A. Lamba, Patient-Specific Stem Cells, 2017
Methyl-CpG binding domain (MBD) is a functional domain that interacts with 5mC DNA and is identified in five proteins, MeCP2 and MBD1, MBD2, MBD3, and MBD4. MeCP2 is especially a critical factor for neuronal development and functions as a transcriptional repressor by recruiting NCoR/SMRT repressive complex (45). Loss of MeCP2 leads to neurodevelopmental disorder, the Rett syndrome (RTT), and several groups, including our laboratory, succeeded in generation of iPSCs from RTT patients (RTT-iPSC) (20,46). RTT-iPSCs show distinguishable transcriptome profiles from normal iPSCs, indicating that MeCP2 also affects transcriptional regulation in the stem cell stage. Furthermore, the deletion of MeCP2 increases the efficiency of iPSC generation (47). Overall, 5mC shows negative effect on iPSC reprogramming but is required to establish stem cells with proper differentiation capacities.
Nano-biosensors: A Custom-built Diagnosis
Published in Paula V. Messina, Luciano A. Benedini, Damián Placente, Tomorrow’s Healthcare by Nano-sized Approaches, 2020
Paula V. Messina, Luciano A. Benedini, Damián Placente
DNA methylation can be visualized using the methyl-CpG-binding domain of the human MBD1 protein. The level and distribution of histone modifications can be monitored by two different methods: (i) fluorescence/Förster resonance energy transfer (FRET)-based sensors and (ii) fluorescent labelled antigen binding fragments of specific antibodies (Kimura et al. 2010). Na Li and co-workers (Li et al. 2012) described a multicolour fluorescence nano-probe that consists of gold nanoparticles (Au NPs) functionalized with a dense shell of recognition sequences (synthetic oligonucleotides) hybridized to three short dye-terminated reporter sequences by gold–thiol bond formation, which simultaneously detects three intracellular tumour-related mRNAs. According to the author’s declaration, the nano-probe is capable of detecting changes in gene expression levels in cancer cells. Another example that caught our attention was the device constructed by Wang et al. (Wang et al. 2012); they fabricated a nano-sensor by decorating gold nanoparticles (AuNPs) with Raman reporters and hemi-methylated DNA probes. They proposed a novel concept for enzymatic control of plasmonic coupling as a surface enhanced Raman scattering (SERS) nano-sensor for DNA demethylation. Demethylation of DNA probes initiates a degradation reaction of the probes by methylation-sensitive endonuclease Bsh 1236I and single-strand selective exonuclease I. This destabilizes AuNPs and mediates the aggregation of AuNPs, generating a strong plasmonic coupling SERS signal in response to DNA demethylation. The authors claimed that the nano-sensor possesses a high signal-to-noise ratio, super specificity, and rapid, convenient, and reproducible detection with homogeneous, single-step operation providing a useful platform for detecting DNA demethylation and related molecular diagnostics and drug screening. Likewise, using a protein labelling technique, Yuichiro Hori and co-workers created a hybrid probe containing a DNA-binding fluorogen and a methylated-DNA-binding domain. The hybrid probe enhanced fluorescence intensity upon binding to methylated DNA and successfully monitored methylated DNA during mitosis (Hori et al. 2018).
Epigenotoxicity: a danger to the future life
Published in Journal of Environmental Science and Health, Part A, 2023
Farzaneh Kefayati, Atoosa Karimi Babaahmadi, Taraneh Mousavi, Mahshid Hodjat, Mohammad Abdollahi
Abnormal and excessive blood pressure in the pulmonary artery causes PHD, eventually leading to right ventricular dysfunction. In recent decades, the importance of epigenetic therapy mediated by DNA methylation alterations and histone modifications has been highlighted in treating lung disease. Using di-methyltransferase SUV4-20H1, knockout mouse caused a PHD phenotype that further confirm the role of histone methyltransferase in the etiology of this disease. The methyl-CpG-binding domain protein family, is a regulatory factor in DNA methylation that was shown to increase in expression in PHD patients’ pulmonary arteries, cigarette smoke (CS)-exposed rat models’ pulmonary arteries, and human pulmonary artery cells exposed to CS, indicating the role of epigenetic modulator in CS-induced PHD. Indeed, epigenetic factors play an essential role in the elevation of blood pressure in the pulmonary arteries (Table 2).[11] According to the previous research, there is a substantial decrease in histone modification of H4K20me2/3 in human patients with COPD, unlike patients with PHD that makes them responsive to epigenetic drug effect.[171] The methylation of H4K20me2/3 was attributed to the activity of the H4K20 di-methyltransferase SUV4-20H1. Smoking or exposure to environmental CS significantly alters gene methylation in COPD-related diseases, especially PHD. One of the regulatory factors of DNA methylation is the methyl-CpG-binding domain protein family (MBD). The MBD2 protein is a factor of the MBD protein family, which acts as a reader in DNA methylation. MBD2 can intervene in transcriptional repression or activation by merging methylated DNA or collecting proteins to form a suppressive combination.[172]