Reducing Aging-associated Risk of Sarcopenia
James M. Rippe in Lifestyle Medicine, 2019
Aging is associated with a genetically programmed loss of body cells. This process, called apoptosis, is often referred to as cell suicide programmed by a biological clock.7,11 Apoptosis results in a noninflammatory-related loss of myocytes as well as of progenitor stem cells and αMN. Acceleration of this process is postulated to play a key role in the etiology of sarcopenia.11 Both biological and environmental factors, which cause gene mutations (i.e., alterations in the nucleotide sequences of gene DNA) and epigenetic (Greek, meaning “above genetics”) alterations are contributors. Epigenetic modifications refer to direct alterations to the DNA and histone protein making up chromatin (e.g., methylation of the DNA or acetylation of the histones).12 Major contributors to both genetic mutations and epigenetic changes, which accelerate apoptosis, are discussed next.
Drugs of Abuse and Addiction
Sahab Uddin, Rashid Mamunur in Advances in Neuropharmacology, 2020
Modifications in histone modification are another type of epigenetic change that modulates the expression of gene, post-translationally. In eukaryotic cells, the genomic material is packed into chromatin, in which the DNA wraps the nucleosome and the histone proteins (H2A, H2B, H3, and H4) becomes the basic unit for structure of the nucleosome along with H1, which spans the non-nucleosomal DNA (Luger et al., 1997). The noncovalent modification of histone proteins at the N-terminal modulates the gene expression via alteration of the chromatin structure to create either a transcriptionally active state (euchromatin) or transcriptionally repressive state (heterochromatin) (Cedar and Bergman, 2009). These dynamic modifications such as phosphorylation, acetylation, sumoylation, ubiquitylation, and methylation are actively mediated by two key enzymes: histone acetyltransferases (HATs) and histone deacetylases (HDACs) (Narlika et al., 2002).
Biological data: The use of -omics in outcome models
Issam El Naqa in A Guide to Outcome Modeling in Radiotherapy and Oncology, 2018
Molecular biology has witnessed rapid growth in recent years due to the extraordinary advances in biotechnology and the success of the Human Genome Project (HGP) and its offshoots. These technologies provide powerful tools to screen a large number of biological molecules and to identify biomarkers that characterize human disease or its response to treatment. These biomarkers follow from the central dogma of biology [199], in which biological information is expressed via the sequential transcription of the DNA genetic code into RNA and subsequent translation of the RNA into proteins, which further interact with intermediaries of metabolic reactions (metabolites) to determine cell function or fate as depicted in figure 6.2. Epigenetic modifications of DNA and associated histone molecules can also contribute an additional layer of regulatory influence on this process [200].
Sirt1 modulates H3 phosphorylation and facilitates osteosarcoma cell autophagy
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Hongliang Ying, Boda Ying, Jinrui Zhang, Daliang Kong
Histone modification is a key type of epigenetic modifications and regulatory mechanisms that affects the structure of chromatin [7]. In general, histone can be phosphorylated, methylated, acetylated, ubiquitinated and ADP-ribosylated [8]. Among them, phosphorylation, especially Histone H3 phosphorylation, is a common and important modification pathway, which is closely related to chromosome condensation during mitosis and transcription [9]. Lee et al. reported that squamocin could regulate H3 phosphorylation and promoted G1 phase arrest and apoptosis of glioma, hepatocellular carcinoma and colon cancer cells [10]. Espino et al. indicated that Ras-MAPK pathway-mediated H3 phosphorylation took part in the development of pancreatic cancer [11]. Until now, no literature can be searched concerning the H3 phosphorylation in osteosarcoma. More experimental researches are still demanded to further probe whether H3 phosphorylation joins in the initiation and progression of osteosarcoma, along with the regulation of histone H3 phosphorylation.
Inhibition of histone demethylase JMJD1C attenuates cardiac hypertrophy and fibrosis induced by angiotensin II
Published in Journal of Receptors and Signal Transduction, 2020
Shenqian Zhang, Ying Lu, Chenyang Jiang
It is well known that histone modifications play key roles in gene transcription. Over the past decades, a great deal has demonstrated that histone methylation plays a key role in cardiac remodeling [7–9]. In our study, we identified a H3K9me2 and H3K9me1 demethylase JMJD1C involved in cardiac hypertrophy and fibrosis induced by pathological stress. JMJD1C is a global regulator of chromatin remodeling and gene expression. Gene expression is mediated by transcription factors and histone-modifying enzymes. Many different histone-modifying enzymes, including HDACs, HATs, HMTs, and HDMs, contribute to the dynamic regulation of chromatin structure and function, with concomitant impacts on gene transcription [28–30]. Unlike transcription factors that often have on-off effects on gene transcription, the effects of histone-modifying enzymes on gene transcription are often modulatory. This modulatory effect can be context- and gene-dependent such that only those genes exceeded the threshold will yield a phenotype and be identified. In our study, we did not identify what genes were different in JMJD1C knockdown and control cells, and which was regulated by histone methylation change. It will be interesting to identify these genes using RNA-seq and ChIP-seq combined analysis to further investigate the relationship between JMJD1C-regulated H3K9me2 marks which ultimately determines the transcriptional state of the gene as either active, repressed, or poised for activation.
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.
Related Knowledge Centers
- DNA
- DNA Repair
- Eukaryote
- Lysine
- Protein
- Cell Nucleus
- Chromatin
- Arginine
- Nucleosome
- Regulation of Gene Expression