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Diagnosis and Pathobiology
Published in Franklyn De Silva, Jane Alcorn, The Elusive Road Towards Effective Cancer Prevention and Treatment, 2023
Franklyn De Silva, Jane Alcorn
About 50% of human cancers have mutations in chromatin proteins [283]. Approximately 6 billion coding and noncoding DNA bases are swaddled around ~30 million nucleosomes assembling an enormous, delicate, and intricately controlled macromolecular complex called ‘chromatin' [283]. The two major regions of chromatin include euchromatin (active genes containing an area with a relatively open configuration), and heterochromatin (late to replicate and highly condensed inactive gene containing area) [302]. Heterochromatin can be further separated into facultative heterochromatin, which encompasses repressed genes in a cell type-specific manner, and constitutive heterochromatin, which mainly encompasses repetitive sequences and transposons positioned at constant areas in different types of cells (e.g., pericentromeric regions) that can be transcribed at minute levels [323]. DNA and histone protein modifications, histone variants, components reading such modifications, noncoding RNAs, chromatin architectural proteins, and components remodeling chromatin, among others, are responsible for regulating the formation and maintenance of heterochromatin [323].
The Precision Medicine Approach in Oncology
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Furthermore, nucleosome occupancy and gene expression activity are influenced by the incorporation of histone variants such as H3.3 and H2A.Z. Histone variants are nonallelic variants of histones which have only one or a few amino acid differences, and are expressed at very low levels compared with their conventional counterparts. Unlike the major histone subtypes, the synthesis and incorporation of these variants into chromatin take place throughout the cell cycle, and not just in S-Phase. However, they undergo post-translational modifications which determine their nuclear localization and function.
Epigenetic Reprogramming of Mammalian Primordial Germ Cells
Published in Cristina Camprubí, Joan Blanco, Epigenetics and Assisted Reproduction, 2018
Sebastian Canovas, Susana M. Chuva de Sousa Lopes
After PGC specification, the majority of promoters become hypomethylated, but this is not directly associated with general transcriptional activation of the respective downstream genes (17,23,43). For further transcriptional regulation, additional mechanisms, such as the remodeling of histone modifications or incorporation of alternative histone variants, are triggered to modulate gene expression.
Epigenetic changes involved in hydroquinone-induced mutations
Published in Toxin Reviews, 2021
Minjuan Zeng, Shaopeng Chen, Ke Zhang, Hairong Liang, Jie Bao, Yuting Chen, Shiheng Zhu, Wei Jiang, Hui Yang, Yixian Wei, Lihao Guo, Huanwen Tang
Phosphorylation of histones and histone variants are generally activation markers associated with an open chromatin structure and genomic instability (Nagelkerke and Span 2016, Ji et al.2017). The phosphorylation of histone H2AX (γ-H2AX) is one of the first steps of the DNA damage response, which is widely found in tumor cells and tissues. Many investigations have shown that the expression of γ-H2AX is increased in TK6 cells treated with HQ (Ling et al.2016, Chen et al.2018, Tan et al.2018). For example, an increase of up to 265% was detected at 3 h in HQ-treated PARP-1-silenced TK6 cells (Ling et al.2016). Peng et al. (2013) showed that γ-H2AX expression increased earlier at 1–6 h but decreased at later exposure time points (12–24 h) in A549 cells exposed to HQ, though the total protein levels of γ-H2AX were significantly increased in U2OS cells exposed to HQ for 4, 6, 8, 12, and 16 h (Yang et al.2019). These results indicate that the phosphorylation of histone H2AX may play different roles in the early and late stages of malignant transformation induced by HQ. As one of the first steps of the DNA damage response, γ-H2AX activates the DNA damage-responsive enzyme, PARP-1, in HQ-induced TK6 cells (Chen et al.2018).
Knocking down miR-384 promotes growth and metastasis of osteosarcoma MG63 cells by targeting SLBP
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
SLBP is an evolutionarily conserved protein and involved in the processing, translation, and degradation of the mRNAs of canonical histones, including H1, H2A, H2B, H3 and H4 [24]. Besides, SLBP is a cell cycle-regulated protein that creates mature histone mRNA by 3’ end cleavage during G1 to S-phase progression [25,26]. Diverse studies have proposed that post-translational histone modification, the deposition of histone variants, and histone chaperones can be also involved in the development of cancers [27–29]. For example, altered expression of many H2A variants is associated with cancer [30]. To our knowledge, the effect of SLBP on cancer diseases has not been investigated. Whether miR-384 indirectly influenced histone modification by regulating SLBP expression should be explored in future studies.
Known epigenetic biomarkers for prostate cancer detection and management: exploring the potential of blood-based liquid biopsies
Published in Expert Review of Molecular Diagnostics, 2019
Vera Constâncio, Daniela Barros-Silva, Carmen Jerónimo, Rui Henrique
In recent years, several epigenetic alterations have been associated with prostate tumorigenesis. Epigenetics refers to heritable and reversible regulatory mechanisms that change gene expression without altering the primary DNA sequence, and the dysregulation of such mechanisms is intrinsically associated with several common diseases, including cancer [11]. The main epigenetic mechanisms studied include DNA methylation, histone post-translational modifications, histone variants, and chromatin remodeling complexes. Epigenetic changes are thought to occur early in tumorigenesis and to accumulate throughout cancer progression. Because some epigenetic alterations may precede the emergence of the malignant phenotype, they represent a valuable marker for cancer screening [11]. Technically, epigenetic marks are robust, sensitive and measurable across individuals. Moreover, their stability in body fluids makes them an attractive target to be studied in liquid biopsies [12].