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Extraction of Sequence-Based Features for Prediction of Methylation Sites in Protein Sequences
Published in Ranjeet Kumar Rout, Saiyed Umer, Sabha Sheikh, Amrit Lal Sangal, Artificial Intelligence Technologies for Computational Biology, 2023
Monika Khandelwal, Nazir Shabbir, Saiyed Umer
Protein methylation shows an important role in several biological and cellular processes, comprising signal transduction, gene regulation, metabolism, RNA processing and gene activation [32, 11]. Protein methylation is a reversible method of post translational modifications (PTM) of proteins. This is a process where methyl groups are added into the proteins by changing the protein sequence to encode more information. There are also other forms of PTM, for instance, ubiquitination [24], sumoylation [51] and phosphorylation [49]. The protein methylation usually occurs at N-terminal side chains of arginine (R) and lysine (K), two main protein methylation sites. This can also occur at histidine (H), asparagine (N), proline (P) and alainine (A). A protein family, methyltransferases, carried out these additions by using S-adenosylmethionine to transfer a methyl group. We are mainly focusing on R and K amino residues, for which publicly data are available and methylation mechanism is best understood.
Introduction to Cancer
Published in Anjana Pandey, Saumya Srivastava, Recent Advances in Cancer Diagnostics and Therapy, 2022
Anjana Pandey, Saumya Srivastava
Unlike the hypomethylation, hypermethylation is a property shown by the specific CpG region only (Bastian et al., 2004; Ellinger et al., 2008; Kvasha et al., 2008; Liu et al., 2010; Xi et al., 2013; Fujii et al., 2015; Skvortsova et al., 2019). Due to that transcriptional inactivation of promoter genes involved in cell repair, cell cycle mechanism, and apoptosis process occurs. This leads to cancer induction (Esteller, 2007), making the hypermethylated promoters as a cancer biomarker for prognostic and diagnostic purposes due to the involvement of CpG regions of mostly promoter genes in hypermethylation. DNA methylation patterns can be disturbed by the impaired functioning of DNMT (DNA methyltransferase) due to getting evidence of higher expressions of DNMT1 and DNMT3b in different tumors (Miremadi et al., 2007).
Enzyme Kinetics and Drugs as Enzyme Inhibitors
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
The above-mentioned hypomethylation promotes the malignant degeneration of cells due to favoring a reorganization of chromosomal sections. The most important mechanism of epigenetic regulation is the methylation of DNA by DNA-methyltransferases. It has been found that hypermethylation (methylation of cytosine residues of DNA) of gene-promoter regions, leading to transcriptional repression of tumor suppressor genes the protein products of which such as CDK-inhibitor 2A and RB1 (retinoblastoma protein) decelerate tumor progression, is a common feature of many cancers (Baylin and Jones, 2011). This also holds for global deacetylation. Histone deacetylases (HDACs) class I, II, and IV are Zn2+-dependent amidohydrolases removing an acetyl moiety from a lysine residue at the N-terminus of histone. Class III HDACs (sirturins) are NAD+-dependent. The catalytic action of HDACs enables the histones to wrap the DNA more tightly whereas acetylation of histones by acetyl transferases (HATs) transferring an acetyl group from acetyl-CoA to form ε-N-acetyl lysine normally results in an increase in gene expression, e.g., that of the tumor suppressor p53. Various HAT families are known that differ from each other in their reaction mechanism. The equilibrium of histone acetylation and deacetylation is important for a proper modulation of chromatin topology and regulation of gene transcription. For an excellent review of exploiting the epigenome to control cancer-promoting gene-expression programs, see Brien et al. (2016).
Adverse health effects and stresses on offspring due to paternal exposure to harmful substances
Published in Critical Reviews in Environmental Science and Technology, 2023
Jiaqi Sun, Miaomiao Teng, Fengchang Wu, Xiaoli Zhao, Yunxia Li, Lihui Zhao, Wentian Zhao, Keng Po Lai, Kenneth Mei Yee Leung, John P. Giesy
The classification of specific epigenetic mechanisms of transgenerational effects is summarized in Table S1. In recent years, increasing evidence has shown that exposure to chemicals and unhealthy living habits of male parents can also affect the phenotype of offspring through sperm-mediated intergenerational inheritance (Chen et al., 2021). Sperm-mediated intergenerational inheritance, which affects phenotypes of offspring, mainly involves methylation of DNA, small noncoding RNAs and modifications of histones (Sales et al., 2017). Methylation of DNA, traditionally considered as a relatively stable modification, is actually a highly dynamic modification that is regulated by methyltransferases and iterative demethylases. Methylation of DNA can be efficiently replicated on daughter strands by maintenance methyltransferase enzymes such as DNA methyltransferase 1 (DNMT1) (Barau et al., 2016). Small noncoding RNAs also participate in the posttranscriptional regulation of gene expression. MiRNAs, small noncoding RNAs of 22 nucleotides, bind to mRNA, ultimately inducing its degradation or inhibiting its translation (Esteller, 2011). Meanwhile, modifications of histones tails at multiple sites provide a potent method for regulation of gene expression. Specific markers, such as monomethylation on lysine 4 of histone H3 (H3K4me1), characterize the active recruitment region and transcription initiation region of the transcription complex, usually on the gene promoter (Creyghton et al., 2010).
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
DNA methyltransferases (DNMTs) are a group of enzymes that transmit a methyl group to the C-5 position of DNA cytosines from their cofactor s-adenosylmethionine via specific reactions. They are classified according to their function into two groups of maintenance enzymes and de novo. De novo DNMTs put methyl groups in places that already lack methyl, while maintenance of DNMTs adds methyl to hemi methyl moieties.[9] DNA methylation also occurs during cell division and is transferred to daughter cells along with the DNA sequence. DNMT1 is responsible for replicating the methylation pattern from the parent to the daughter string. As a maintenance methyltransferase, this enzyme is associated with hemimethylated DNA, showing signs of methylation in only one strand. DNMT1 also binds to hemimethylated DNA and helps methylate the daughter strand to recover fully methylated CpG dinucleotides. Thus, DNMT1 maintains the stability of this epigenetic mark across different generations. Methylated CPGs may bind to methyl-CPG proteins associated with methyl CpG binding proteins 1 and 2 (MECP1 and MECP2 (MBDs)), which can alter transcription. Methylated DNA harbors additional proteins known as methyl-CpG binding domain proteins, which interact with other proteins such as histone deacetylase (HDAC) and thus create compressed and inactive chromatin.[11] DNA methylation by DNA de novo 3 A (DNMT3A) and 3B (DNMT3B) methyltransferases is essential for genome regulation. Irregularities in the activity of these enzymes cause various diseases, especially cancer. DNMT3A is significant for establishing patterns for DNA methylation during development before birth.[12]
Association of liver and kidney functions with Klotho gene methylation in a population environment exposed to cadmium in China
Published in International Journal of Environmental Health Research, 2020
Dongmei Yu, Li’e Zhang, Guoqi Yu, Chuntao Nong, Mingzhi Lei, Jiexia Tang, Quanhui Chen, Jiangsheng Cai, Shiyi Chen, Yi Wei, Xia Xu, Xu Tang, Yunfeng Zou, Jian Qin
DNA methylation is a highly important epigenetic modification that regulates the expression of genes in the body. DNA methylation refers to the methyl donation by S-adenosylmethionine under the action of DNA methyltransferases (DNMTs). The methyl group is transferred to the fifth carbon atom of the deoxycytosine ring and causes the covalent modification of methylated cytosine (Re and Ji 2002). Many studies have reported the effects of cadmium on the DNA methylation of different genes, but a good linear correlation between cadmium exposure level and Klotho methylation level was not achieved in the present research. Cadmium is currently known to inhibit the viability of DNMTs in eukaryotes and prokaryotes. Poirer and Vlasova reported that the concentration of Cd2+ (1–500 μmol/L) is negatively correlated with the activity of DNMT (Poirer and Vlasova 2002). This correlation may explain that why elevated cadmium exposure levels lead to a decreased Klotho methylation levels. Age has a certain impact on DNA methylation (Jones et al. 2015); the average ages of the Luoma, Chehe and Pingcun participants were 47.89, 42.03 and 45.90 years, respectively (p < 0.001). Relatively low age also explains why Chehe’s participants attained the lowest level of Klotho methylation. Some scholars have studied the effect of cadmium on DNMT activity and observed DNMT activity to be substantially inhibited dose dependently after 0–0.25 μmol/L Cd2+ exposure for 1 week. However, after 10 weeks’ exposure, the activity of DNMT rose, and the genomic methylation level increased (Vandegehuchte et al. 2009). Similarly, Tallaa et al. used cadmium to induce malignant cell transformation for 10 weeks and found progressive increases in generalized DNMT enzymatic activity (Benbrahim-Tallaa et al. 2007). Even so, the specific mechanisms of the above process remain unclear. Some scholars have speculated that this mechanism may increase with the compensatory expression of DNMT. This notion means that low levels of cadmium exposure can reduce Klotho methylation levels, and high levels of cadmium exposure can increase Klotho methylation levels. This relation is consistent with that reported above.