The Emerging Role of Histone Deacetylase Inhibitors in the Treatment of Lymphoma
Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey in 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.
Pantothenic Acid and Biotin
Judy A. Driskell, Ira Wolinsky in Sports Nutrition, 2005
Chromatin comprises (1) DNA; (2) a group of proteins named histones; and (3) various non-histone proteins. The folding of DNA into chromatin is mediated primarily by histones.34 Five major classes of histones have been identified in mammals: H1, H2A, H2B, H3 and H4. Histones consist of a globular domain and a more flexible and charged amino terminus (histone “tail”). Lysines, arginines, serines and glutamates in the amino terminus are targets for acetylation, methylation, phosphorylation, ubiquitination, poly (ADP-ribosylation) and sumoylation.13,34–37 These modifications of histones regulate processes such as gene expression, replication and DNA repair.34 All five classes of histones are also modified by covalent attachment of biotin.38–40 Biotinylation of histones is mediated by biotinidase 38 and holocarboxylase synthetase.41 Evidence has been provided that biotinylation of histones might play a role in gene silencing and in the cellular response to DNA damage.40–43
Role of Histones in Cell Differentiation
Gerald M. Kolodny in Eukaryotic Gene Regulation, 2018
A new technique of gel electrophoresis in the presence of Triton® X100 has led to a discovery which may turn out to be of essential significance for the problem of cell differentiation. This technique has shown that all histone species in animals, with the exception of H4, are represented by several variants (isohistones) — two for H2a, three for H2b, and three for H3.38–40c Three molecular species of H2a were found in rat chloroleukemic cells.41 The histone variants differ by several amino acid substitutions, mainly in their hydrophobic regions. The presence of two forms of H3 in calf thymus — one minor component (20% with only one cysteine residue and a major component with two cysteine residues — has already been shown.42 It is important that the histone variants were found to be nonallelic and present in all tissues in different relative amounts.39
Maintaining a ‘fit’ immune system: the role of vaccines
Published in Expert Review of Vaccines, 2023
Béatrice Laupèze, T. Mark Doherty
Modification of histones is an important mechanism underlying ‘trained immunity’ [24]. Histones are structural proteins that wrap DNA into a condensed form (nucleosomes) in the nucleus. Modifications to the histone tail by acetylation of lysine or methylation of lysine or arginine have opposing actions on the architecture of the surrounding chromatin, making it easier or harder for the protein complexes involved in transcription to access gene promoter regions, respectively, thus leading to increased or decreased transcription [23]. Acetylation (generally linked to increased transcription) and methylation (generally linked to decreased transcription), at the extremes can promote a state of hyper-inflammation or immune tolerance, respectively [23,25]. Long-term changes to myeloid cell populations can be brought about by epigenetic, transcriptomic, and functional reprogramming of myeloid stem cells in the bone marrow.
KRas-ERK signalling promotes the onset and maintenance of uveal melanoma through regulating JMJD6-mediated H2A.X phosphorylation at tyrosine 39
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Yaping Li, Peng Yu, Ying Zou, Wenrui Cai, Weixuan Sun, Ning Han
Epigenetics is a science that studies the change of heritable phenotype, while the DNA sequence of the genome is unaltered. The heritable phenotype changes mainly comprise histone modification, DNA methylation and non-coding RNA regulation [3]. There are five subtypes of histone: H1, H2A, H2B, H3 and H4. It has been mentioned that histone modification is an epigenetic mechanism that is closely associated with carcinogenesis [5]. H2A.X, an element of histone H2A family, locates downstream of the DNA damage kinase signalling cascade [6]. Histone H2A.X phosphorylation on serine 139, also called γ-H2A.X, is a key indicator of DNA damage [7]. It has been proved that histone H2A.X on tyrosine 39 (H2A.XY39ph) is a prerequisite for γ-H2A.X formation [8]. While recent studies have pointed out that H2A.X has a tumour suppressive function by avoiding genome unstablity and acts as a biomarker for detecting DNA damage during therapy [9,10], the exact function of H2A.XY39ph in cancer is still unclear.
Ras-PI3K pathway promotes osteosarcoma progression via regulating VRK1-mediated H2A phosphorylation at threonine 120
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Xianlun Xu, Hao Yu
Osteosarcoma, deriving from the aberrant growth of primitive bone-forming mesenchymal cells, is the most common malignant bone tumour in children and adolescents [1,2]. Ras-phosphatidylinositol 3-kinase (PI3K) pathway aberrant activation plays an important role in the occurrence and development of osteosarcoma [3,4]. It is proved that Ras-PI3K pathway takes part in the modulation of multiple osteosarcoma cellular biological processes [4,5]. A number of genes that exert critical regulatory activities in cell proliferation and metastasis are the downstream target genes of Ras-PI3K pathway in cells [6,7]. However, there is little information available about the definite effects of Ras-PI3K pathway activation on epigenetic changes of osteosarcoma cells. Histone modification is a common epigenetic change, which consists of methylation, acetylation, phosphorylation, ubiquitination and adenosine-diphosphate (ADP)-ribosylation [8,9]. There are generally five subtypes of histone in eukaryotic cells: H1, H2A, H2B, H3 and H4 [10]. Histone H2A phosphorylated at threonine 120 (H2AT120ph) is a key histone phosphorylation pathway in cells [11]. Kim et al. reported that H2AT120ph is involved in the regulation of multiple tumour suppressor genes transcriptions in many cancer cells, such as bladder cancer, breast cancer and prostate cancer [12]. However, the effects of H2AT120ph on the gene transcription of osteosarcoma cells remain unclear.
Related Knowledge Centers
- DNA
- DNA Repair
- Eukaryote
- Lysine
- Protein
- Cell Nucleus
- Chromatin
- Arginine
- Nucleosome
- Regulation of Gene Expression