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The Parasite's Way of Life
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
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.
Naturally Occurring Histone Deacetylase (HDAC) Inhibitors in the Treatment of Cancers
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Sujatha Puttalingaiah, Murthy V. Greeshma, Mahadevaswamy G. Kuruburu, Venugopal R. Bovilla, SubbaRao V. Madhunapantula
Modification of histones is one of the key epigenetic mechanisms implicated in the regulation of gene expression (Stephens et al., 2013). Acetylation and deacetylation reactions catalyzed by HATs and HDACs play an important role in mediating the unpacking and packing of DNA, thereby improving gene function (Shahbazian and Grunstein, 2007). HDACs remove the acetyl groups from histone and non-histone proteins, thereby controlling the expression of genes (Parbin et al., 2014). To date, 18 HDACs have been identified and characterized for their structure and function (Figure 8.1B) (Ropero and Esteller, 2007).
Mother and Embryo Cross Communication during Conception
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Anna Idelevich, Andrea Peralta, Felipe Vilella
Histone modification is another epigenetic mechanism. Histones are basic proteins acting as spools around which DNA winds, packaging it into structural units, called nucleosomes. A histone octamer consisting of two copies of each of the four core histones (H2A, H2B, H3, and H4), around which approximately 146 bp of the DNA winds, comprises a nucleosome. It has been shown that histones are subject to numerous covalent modifications, including methylation, acetylation, phosphorylation, sumoylation, glycosylation, and ubiquitination, at specific tails of selected amino acids. A number of enzymes are involved in this process, including histone methyltransferases (HMTs), acetyltransferases (HATs), kinases, and ubiquitin ligases functioning as writers, as well as erasers, such as histone demethylases, deacetylases (HDACs), and phosphatases, capable of removing modification marks from the histone tails. These modifications impose either transcriptionally repressive or transcriptionally permissive chromatin structures. For instance, histone acetylation usually results in active genes as does the di- or trimethylation of lysine residue 4 in histone H3 (H3K4me2, H3K4me3), whereas H3K9me2/3 and H3K27me3 modifications repress gene expression. In general, unlike DNA methylation, which is believed to confer a more stable and long-term silencing mechanism, various histone modifications seem to exert short-term, flexible regulation important for the plasticity of development [140–144].
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.
Histone deacetylase inhibitors as a potential new treatment for psoriatic disease and other inflammatory conditions
Published in Critical Reviews in Clinical Laboratory Sciences, 2023
Jehan Mohammad Nazri, Katerina Oikonomopoulou, Elvin D. de Araujo, Dziyana Kraskouskaya, Patrick T. Gunning, Vinod Chandran
As mentioned previously, HDACs are enzymes that function to remove acetyl groups from lysine residues of proteins in a process called deacetylation. These proteins, also known as substrates, can be classified as either histone or non-histone. Briefly, in humans, there have been four families of histones identified: H1, H2 (H2A and H2B), H3, and H4. Early studies demonstrated that HDAC1, HDAC2, HDAC4, HDAC5, and HDAC6 all lack specificity and were able to deacetylate all four core histone proteins, that is, H2A, H2B, H3, and H4 [116]. However, later experimental results indicate that there may be an issue of substrate specificity and preference by HDACs when it comes to deacetylating histones, although this is yet to be fully established [117,118]. For instance, HDAC6 has now been found to have no in vivo activity against histones by way of nuclear deacetylation [119], while HDACs 4, 5, and 7 all show low activity in their catalytic domains [120]. Similarly, non-histone substrates of HDACs are also the subject of intense study. To date, a comprehensive list of non-histone substrates for each HDAC and their specific functional consequences have not been fully characterized although several studies have identified some non-histone substrates for a few HDACs [115,121–123]. Among these non-histone substrates identified are transcription factors, hormone receptors, signal transducers, chaperone proteins, and proteins of the cytoskeleton network.
How to treat histone 3 altered gliomas: molecular landscape and therapeutic developments
Published in Expert Review of Clinical Pharmacology, 2023
Vincenzo Di Nunno, Enrico Franceschi, Lidia Gatto, Alicia Tosoni, Stefania Bartolini, Alba Ariela Brandes
The lysine to methionine mutation (K27M) occurring in the K27 residue is the hallmark of the diagnosis of DMG [1]. This mutation can occur in different gene variants encoding the histone 3 (H3) protein [11]. These variants are the H3F3A (H3.3), the HIST1H3B/C (H3.1), or HIST1H3B/D (H3.2). The H3 protein encoded by the H3.3 gene is expressed constitutively during the cell cycle, whereas the H3.1 protein is specifically expressed during the S-phase [12]. The K27M mutation occurs more frequently on the H3.3 gene since it can be detected in about 80% of pediatric and 15–60% of adult DMG [13,14]. The remaining DMG cases are conducible to a K27M mutation occurring on the H3.1 gene [13,14], or overexpression of the Enhancer of Zest Homologs Inhibitory Protein (EZHIP) with wild-type H3 protein [15,16]. The K27M mutation occurring on the H3.2 gene is extremely rare [14].