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Epigenetic Alterations in Alzheimer’s Disease and Its Therapeutic and Dietary Interventions
Published in Atanu Bhattacharjee, Akula Ramakrishna, Magisetty Obulesu, Phytomedicine and Alzheimer’s Disease, 2020
P. M. Aswathy, C. M. Shafeeque, Moinak Banerjee
Nucleosomes are the fundamental units of chromatin, and each nucleosome is composed of 147 DNA base pairs, wrapped tightly around an octamer of histone proteins, which consists of two copies of each of the four core histones, H2A, H2B, H3, and H4. The linker histone, H1, binds to the DNA between the nucleosomal core particles, and is essential to stabilize higher-order chromatin structures. Each histone protein consists of a central globular domain and an N-terminal tail that contains multiple sites for various post-translational modifications (Bowman and Poirier 2015), such as acetylation, methylation, phosphorylation, ADP-ribosylation, ubiquitylation, sumoylation, crotonylation, propionylation, deimination, and O-GlcNAcylation (Sanchez-Mut and Gräff 2015). These modifications can occur on different amino acids; lysines can be acetylated, methylated, ubiquitylated, or sumoylated, arginines can be deiminated, methylated, or ADP-ribosylated, histidine residues can be methylated, and serine or threonine residues can be phosphorylated or O-GlcNAcylated, whereas glutamate residues can be ADP-ribosylated, tyrosines can be phosphorylated, and prolines can be isomerized (Hanes 2015; Xu et al. 2014; Bowman and Poirier 2015).
The Emerging Role of Histone Deacetylase Inhibitors in the Treatment of Lymphoma
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
Histones are the major structural proteins around which more than 2 m of DNA in every eukaryotic cell is organized. These proteins are considered to be small molecular weight proteins composed of a very high proportion of positively charged amino acids like lysine and arginine. This complex of histone protein, nonhistone protein, and DNA is often referred to as chromatin, the fundamental unit of which is referred to as the nucleosome. The nucleosome consists of a complex of approximately 150 bp of DNA and a histone octamer. Each histone octamer is comprised of a pair of histones including H2A, H2B, H3, and H4 (Fig. 1). Neighboring nucleosomes are linked together by DNA bound to the linker histone (H1). This complex assembly of protein and DNA provides an important organizational structure that helps the cell maintain control over transcription.
Notes on Genetic and Radiation Control of Senescence
Published in Nate F. Cardarelli, The Thymus in Health and Senescence, 2019
Each of the five major histones may be fractionated into a group of slightly different compounds. From the view of the thesis of this text, histone H1 promises to be of considerable interest, since it is not normally a part of the nucleosome. Unlike the others, H1 subfractions show pronounced variation during phylogenesis.45,46 In 1974 Appels et al. found that H1 depletion will stop DNA synthesis of reactivated chick erythrocyte nuclei (from chicken/HeLa heterokaryons).47 Chiu et al. noted that H1 was absent in transcriptionally active chromatin in vitro.48 Others have confirmed this absence.49 Thus, it can reasonably be concluded that the presence of H1 suppresses gene expression, and absence allows it.
In vitro cytotoxicity of polyphenols from Datura innoxia aqueous leaf-extract on human leukemia K562 cells: DNA and nuclear proteins as targets
Published in Drug and Chemical Toxicology, 2020
Elham Chamani, Roshanak Ebrahimi, Khatereh Khorsandi, Azadeh Meshkini, Asghar Zarban, Gholamreza Sharifzadeh
Studies have shown that DNA is a pharmacological target of many of the drugs currently in clinical use or in advanced clinical trials (Hurley and Boyd 1988, Sirajuddin et al. 2013). In the eukaryotes, nuclear DNA interacts with histone proteins and forms a nucleoprotein complex known as chromatin. Chromatin arranges the nuclear genome into a restricted volume. The first level of chromatin organization consists of DNA-folding around histone proteins to shape the fundamental unit of the chromatin, the nucleosome (Hübner et al. 2013). In a nucleosome, 147 bp of DNA are enfolded in an octamer with two copies of four core histone proteins (H2A, H2B, H3, and H4) (Nair and Kumar 2012). As a linker histone, histone H1 surrounds the chromatosome by protecting the internucleosomal linker DNA near the nucleosome entry-exit point (Dixon et al. 2016, Kalashnikova et al. 2016).
The role of pharmacogenomics in adverse drug reactions
Published in Expert Review of Clinical Pharmacology, 2019
Ramón Cacabelos, Natalia Cacabelos, Juan C. Carril
Histones are nucleosomic proteins integrated in the nuclear chromatin. Nucleosomes are formed by 147 DNA base pairs wrapped around an octamer of histones, assembled by two copies of each of the four core histones, H2A, H2B, H3, and H4. Histone H1 is the linker binding DNA between the nucleosomal core particles to stabilize chromatin structures. Histones are formed by a central globular domain and an N-terminal tail with multiple sites for modification of nucleosomal organization, leading to ATP-dependent chromatin remodeling complexes and post-translation amino acid modifications on histone tails. Histone modifications (HMs) are essential epigenetic features, with fundamental roles in biological processes such as transcription, DNA repair and DNA replication. Histone acetylation is achieved by the action of histone acetyltransferase (HAT), which adds an acetyl group to a lysine residue, resulting in chromatin/transcriptional activation; histone deacetylation is produced by histone deacetylases (HDACs) which remove the acetyl groups, and is related to chromatin inactivation and transcriptional repression [27].
Emerging DNA methylation inhibitors for cancer therapy: challenges and prospects
Published in Expert Review of Precision Medicine and Drug Development, 2019
Aurora Gonzalez-Fierro, Alfonso Dueñas-González
The human genome is organized into 23 chromosomes so that each diploid cell with 46 chromosomes contains approximately 6 billion base pairs of DNA. If this DNA would be in a linearized form, each cell would have around 2-m length of DNA. Such amount of DNA must be packaged into the nucleus; hence, histone proteins mainly are responsible for organizing the long fibers of DNA within the nucleus. Both, the DNA complexed with histones are the elements of chromatin and the nucleosome is considered the functional unit of the genome. Nucleosomes are formed by a histone octamer formed by dimers of H2A, H2B, H3, and H4 which are linked by histone H1. Approximately 147 bp of superhelical DNA is wrapped around the histone octamer forming the nucleosome core particle [3]. Epigenetics, therefore, can be referred to as the study of all the elements involved in the regulation of nucleosome. Functionally, these elements are highly interacting in order to respond to the cells’ needs for proper regulation of gene expression in a time and cell-specific manner.