The Parasite's Way of Life
Eric S. Loker, Bruce V. Hofkin in Parasitology, 2023
As discussed in Chapter 2 (see Figure 2.34) histones are an especially important type of DNA-associated protein found in chromatin. The addition of methyl groups (methylation) to histone proteins is well-known as a mechanism that regulates whether associated DNA is in the heterochromatin or euchromatin form. Methyl groups are added to specific amino acid residues by a group of enzymes called methyltransferases. Histone methylation can either increase or decrease transcription of genes, depending on which amino acids in the histones are methylated and how many methyl groups are added. Methylation events that weaken chemical attractions between histones and DNA increase transcription because they enable the DNA to uncoil, allowing transcription factors and RNA polymerase to access the DNA.
Statistical Considerations and Biological Mechanisms Underlying Individual Differences in Adaptations to Exercise Training
Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse in The Routledge Handbook on Biochemistry of Exercise, 2020
The term epigenetics translates to “in addition to changes in genetic sequence” and refers to chemical modifications to DNA (such as DNA methylation) that regulate the expression of genes without altering the underlying DNA sequence, which can ultimately result in downstream changes in protein expression (10). There are two main types of epigenetic modifications (37). First, DNA methylation involves the addition of methyl groups directly to the DNA sequence by DNA methyltransferases (50). DNA methylation results in decreased transcription of the targeted gene, whereas DNA demethylation (or hypomethylation), a process regulated by ten-eleven translocation enzymes (50), increases gene transcription (see 58 for details). The second epigenetic process is histone modification, which involves post-translational modifications to histones (the protein forming the nucleosome core and providing structural stability) that ultimately affect transcription by allowing or inhibiting the transcriptional machinery access to promoter regions of target genes (50). Although not often considered an epigenetic process (37), the actions of non-coding RNAs (such as micro RNA) can also influence gene expression without altering DNA sequence. Collectively, DNA (de)methylation, histone modification, and non-coding RNAs influence gene expression and may therefore play important roles in the adaptive process to exercise (37, 50, 83, 85).
Introduction to Genomics
Altuna Akalin in Computational Genomics with R, 2020
DNA methylation is usually associated with gene silencing. DNA methyltransferase enzyme catalyzes the addition of a methyl group to cytosine of CpG dinucleotides (while in mammals the addition of methyl group is largely restricted to CpG dinucleotides, methylation can occur in other bases as well). This covalent modification either interferes with transcription factor binding on the region, or methyl-CpG binding proteins induce the spread of repressive chromatin domains, thus the gene is silenced if its promoter has methylated CG dinucleotides. DNA methylation usually occurs in repeat sequences to repress transposable elements. These elements, when active, can jump around and insert them to random parts of the genome, potentially disrupting the genomic functions.
A 5-gene DNA methylation signature is a promising prognostic biomarker for early-stage cervical cancer
Published in Journal of Obstetrics and Gynaecology, 2022
Hongxia Chen, Hongying Li, Lei Wang, Yaxiong Li, ChunYan Yang
DNA methylation, a kind of epigenetic modification, may regulate gene expression and chromatin structure via DNA methyltransferase and demethylation enzymes (Li et al. 2017). It has been widely involved in the tumourigenesis and development of CC. For instance, HPV-mediated DNA methylation has been found in the aetiology of CC (Verlaat et al. 2018). The changes of gene expression due to DNA methylation have been widely observed in CC as well, including secreted frizzled-related proteins (SFRPs) (Lin et al. 2009), death-associated protein kinase 1 (DAPK-1), retinoic acid receptor beta (RARB), O6-methylguanine DNA methyltransferase (MGMT) (Sun et al. 2015), etc. Based on these novel findings, several gene methylation signatures could be used for risk stratification and early prognoses of CC patients. For example, Cai et al. (2020) identified a risk model that included a 10-gene methylation, which could discriminate CC patients of pathological stages I–III at different risk of mortality. Xu et al. (2019) identified four CC-specific methylation markers that were capable of distinguishing CC from normal tissues. Furthermore, Brebi et al. also revealed that the methylated changes of five genes could differentiate between CC and normal samples. Despite these remarkable findings, research on the DNA methylation signatures used for early-stage CC’s clinical prognosis was still limited.
DNA methyltransferase inhibitors increase NOD-like receptor activity and expression in a monocytic cell line
Published in Immunopharmacology and Immunotoxicology, 2022
Claire L. Feerick, Declan P. McKernan
DNA methylation and histone acetylation are the best-characterized contributors to the epigenome [17,18] and so are investigated here. DNA methylation, catalyzed by DNA methyltransferase enzymes, involves the addition of a methyl group onto cytosine residues, forming 5-methylcytosine [19]. It is generally accepted that methylation of cytosines in CpG dinucleotides-rich regions, referred to as ‘CpG islands,’ within the transcriptional start sites (TSSs) silences the downstream gene [17]. Histone acetylation is the addition of acetyl groups to lysine residues in histone proteins thereby neutralizing lysine’s positive charge, reducing their affinity for surrounding DNA, and thereby relaxing the chromatin and accommodating expression of underlying genes [20]. Histone acetylation status is maintained by a balance in the activity of two enzymes; histone acetyltransferases (HATs) and histone deacetylases (HDACs) [21]. Drugs targeting epigenetic modifying enzymes have recently been used in the treatment of certain cancers but the full extent of their effects have not been studied [22–26]. Previous work from our group has shown that pharmacological and genetic inhibition of such enzymes affected TLR responses in intestinal epithelial cells [27]. We hypothesized that drugs targeting epigenetic modifications may regulate NOD1/2 expression and pro-inflammatory activity in a monocytic cell line.
Plazomicin: an intravenous aminoglycoside antibacterial for the treatment of complicated urinary tract infections
Published in Expert Review of Anti-infective Therapy, 2020
Anastasia Bilinskaya, Kristin E. Linder, Joseph L. Kuti
Aminoglycoside resistance in Enterobacterales is largely attributed to mobile genes coding for aminoglycoside modifying enzymes (AME), which inactivate the antibiotic molecule, and alterations of the ribosomal target by specific methyltransferases, which prevent aminoglycosides from binding to the ribosome [12]. AMEs are divided into three subclasses based on the type of chemical modification they are responsible for: N-acetyltransferases (AAC), O-nucleotidyltransferase (ANT), and O-phosphotransferases (APH) [13]. AAC acetylates amino groups via acetyl co-enzyme A, ANT adenylates hydroxyl groups, and APH is responsible for the phosphorylation of hydroxyl groups [12,14]. AMEs are further characterized based on the position number of the modification. For example, acetylation of amino groups at position 6ʹ would equate to AAC(6ʹ) based on the Shaw classification system [15]. Although there are over fifty different AME genes, the most well-recognized and clinically relevant genetic variant in Enterobacterales is the AAC(6ʹ)-1b gene [16]. In addition to AMEs, plasmid-borne 16S rRNA methyltransferases have been identified, albeit rarely, in Enterobacterales. These methyltransferases are responsible for the addition of methyl groups to the aminoacyl-tRNA recognition site, or A-site, ultimately protecting the ribosome from aminoglycoside binding. The armA and rmtB genetic variants are among the most commonly identified in Enterobacterales and confer high-level resistance to amikacin, gentamicin, and tobramycin [12].
Related Knowledge Centers
- Epigenetics
- Genomic Imprinting
- Histone Methyltransferase
- Methionine
- Methylation
- Rossmann Fold
- S-Adenosyl Methionine
- Natural Product
- S-Adenosyl-L-Homocysteine
- Transcription