China
Africa
Explore chapters and articles related to this topic
Epigenetics from Oocytes to Embryos
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Dagnė Daškevičiūtė, Marta Sanchez-Delgado, David Monk
Even though nuclear exclusion of DNMT1 is essential for passive demethylation in cleavage-stage embryos, genetic evidence implies it is still required for maintenance of ICR methylation, suggesting that it is not exclusively retained in the cytoplasm. The limited amounts of DNMT1, as well as DNMT3A/B, are targeted to ICR via the TRIM28/KAP1 co-repressive complex that exhibits sequence-specificity due to the zinc-finger proteins (ZFPs) ZFP57 and ZNF44531–34 (Figure 9.2c). Classically, ZFP-KAP1 complexes include the TRIM28/KAP1 scaffold protein, the histone methyltransferase SETDB1, the nucleosome remodeling histone deacetylation complex (NuRD), heterochromatin protein 1 (HP1), and the DNA methylation machinery, all of which are responsible for silencing of transposable elements, with underlying sequence-specificity attributed to unique combinations of ZFPs that target different retrotransposon families.35 Once recruited to a sequence, transcriptional repression is mediated by H3K9me3 and DNA methylation.36 ZFPs have been shown not only to recognize transposable elements, but an increasing number of these proteins also bind to single-copy regions in the genome as highlighted by ZFP57 and ZNF445.33,34
Role of Histone Methyltransferase in Breast Cancer
Published in Meenu Gupta, Rachna Jain, Arun Solanki, Fadi Al-Turjman, Cancer Prediction for Industrial IoT 4.0: A Machine Learning Perspective, 2021
Surekha Manhas, Zaved Ahmed Khan
Gene expression regulation by means of histone-modifying enzymes marks a dominant mechanism that regulates the differentiation and development of cells. Posttranslationally, modifications of histones could be carried out by methylation, acetylation, phosphorylation, ubiquitination, and sumoylation [75]. In particular, methylation at lysine residues of histone protein is the chief regulator of active gene expression. MLL1-dependent H3K4me3 and EZH2-dependent H3K27me3 EZH2, H3K27me3, are the foremost well-known modifications that are strongly related to recognizable gene expression also with repression [76–80]. Various other specific histone-methylation regions have been recognized to be more critical, including H3K9 histone residue with G9a-dependent H3K9me2 and Suv39h (1–2)-mediated H3K9me3. All these display crucial functional roles in cellular differentiation and functions, too [81–84]. Available data suggest that H3K9me2 has also been found to modify euchromatin. In addition, it also is dynamically able to regulate the gene expression of many differentiating cells.
Epigenetic Reprogramming in Early Embryo Development
Published in Cristina Camprubí, Joan Blanco, Epigenetics and Assisted Reproduction, 2018
Histones are proteins that associate with DNA to package chromatin into nucleosomes which allows DNA condensation but also restricts access of regulatory factors to the DNA strand, affecting transcription. Histone tails are exposed on the nucleosome surface and they can be modified by addition of different molecules (acetylation, methylation, but also ubiquitination, SUMOylation, and phosphorylation) which alters the chromatin structure and increase or reduce its accessibility, according with the specific residue and/or the number of molecules that are added to histone amino acids. Histone tails modifications can correlate with different biological effects including DNA repression or activation, and configure a complex marking system called “histone code” (80,81). For example, histone acetylation affects chromatin structure (by decreasing interaction between positive charges on the histones and the negatively charged DNA) and facilitates the access of transcription factors to DNA. However, according with position and the number of methyl groups that are added to histone tails, it can correlate with either silencing (H3K9me3 and H3K27me3) or with activation (H3K4me3, H3K36me3) of DNA. But also histones modifications are connected to DNA methylation machinery or even protection of DNA from demethylation (82).
Enterotoxigenic Bacteroides fragilis induces the stemness in colorectal cancer via upregulating histone demethylase JMJD2B
Published in Gut Microbes, 2020
Qian-Qian Liu, Chun-Min Li, Lin-Na Fu, Hao-Lian Wang, Juan Tan, Yun-Qian Wang, Dan-Feng Sun, Qin-Yan Gao, Ying-Xuan Chen, Jing-Yuan Fang
We subsequently explored the molecular mechanism by which ETBF induces CRC cells stemness. Changes in the intestinal microenvironment, such as dysbacteriosis, can cause histone modifications and chromatin structure alterations by recruiting or retrieving chromatin-modifying enzymes.40,41 H3K9me3 is a hallmark of gene transcriptional repression regions. Expression activation of the stemness maintainers NANOG and SOX2 are regulated by H3K9me3 demethylation.42,43 The histone demethylase JMJD2 is the only member of gene family that can remove H3K9me3, and its members include JMJD2A, JMJD2B, JMJD2C, and JMJD2D. Compelling evidence indicates that JMJD2B is overexpressed in human CRC tissue, and that it is implicated in various cellular processes, including apoptosis, cell cycle, invasion, DNA damage response, and metabolism to promote CRC progression.44–47 Furthermore, JMJD2B plays a critical role in self-renewal of ESCs and iPSC generation.48,49 Consequently, we hypothesized that ETBF promotes CRC stemness via JMJD2B. In support of this, we found that genetic inhibition of JMJD2B in ETBF-co-cultured cells inhibited sphere formation and NANOG expression. Furthermore, ETBF-induced pro-tumorigenicity effect was reversed using JMJD2B shRNA in the tumor bearing mouse models. ChIP data revealed high occupancies of H3K9me3 in the promoters of NANOG, and JMJD2B could transcriptionally upregulate the expression of NANOG by binding and removing the inhibitory H3K9me3 in the NANOG promoter region.
A systems biology approach to antimalarial drug discovery
Published in Expert Opinion on Drug Discovery, 2018
Wilian Augusto Cortopassi, Tanos Celmar Costa Franca, Antoniana Ursine Krettli
P. falciparum is able to bind to the intravascular host cell receptors through the major adhesion surface protein PfEMP1, which is encoded by 60 genes belonging to the var family. Only a single gene is expressed at a given time, and it alternates among other members of the family [74]. This is a well-understood mechanism by which the parasite avoids immune clearance. Different epigenetic modifications are shown to correlate with this gene activation/deactivation mechanism in P. falciparum. Di- and tri-methylation of lysine 4 of histone 3 (H3K4me2 and K3K4me3, respectively), as well as acetylation of lysine 9 of histone 3 (H3K9ac), are associated with activated genes, while silenced genes are enriched in tri-methylated lysine 9 of histone 3 (H3K9me3) [75,76]. Epigenetic eraser regulators such as PfSIR2A are responsible for the removal of the acetyl group of histone 3 (H3K9ac) and therefore are implicated in silencing of the var genes [77]. Other epigenetic proteins are also shown to have roles in gametocyte production. Heterochromatin protein 1 (PfHP1) is an epigenetic reader regulator that is able to bind to H3K9me3. Depletion of this gene results in gametocyte production, suggesting that proteins in the H3K9 tri-methylation pathway are potential targets for blocking parasite transmission to mosquitoes, although specificity for Plasmodium epigenetic regulators may also emerge as a challenge before these preclinical studies advance to clinical trials [78].
Effect of titanium dioxide nanoparticles on histone modifications and histone modifying enzymes expression in human cell lines
Published in Nanotoxicology, 2022
Marta Pogribna, Beverly Word, Beverly Lyn-Cook, George Hammons
Histone H3 lysine 9 trimethylation (H3K9me3) is a crucial epigenetic mark of heterochromatin and has been associated with transcriptional repression (Baylin and Jones 2011). H3K9me3 has roles in regulating apoptosis, autophagy, development, DNA repair, splicing, self-renewal, transcriptional elongation, viral latency, imprinting, aging, and cell identity (Monaghan et al. 2019). An increase in H3K9 methylation, leading to aberrant gene silencing, has been found in various forms of cancer (Nguyen et al. 2002; Park et al. 2008). The level of H3K9me3 is upregulated in invasive regions of colorectal cancer tissues and H3K9 trimethylation was positively related to lymph node metastasis (Yokoyama et al. 2013). Increased trimethylation of H3K9me3 is commonly observed in human lung cancer (Langevin, Kratzke, and Kelsey 2015). A decrease in H3K9me3 is also associated with better prognosis in patients with acute myeloid leukemia (Müller-Tidow et al. 2010). Trimethylation of histone H3 at lysine 4 (H3K4me3) is associated with transcriptional competence and activation, with the highest levels observed near transcriptional start sites of highly expressed genes (Shi et al. 2004). A decrease of H3K4me3 has been observed in several neoplastic tissues (Seligson et al. 2009). In contrast, higher expression of H3K4me3 was associated with shorter survival and higher chances of tumor recurrence in the early stages of colon cancer (Benard et al. 2014). Additionally, a recent meta-analysis of patients with malignant tumors indicated that increased H3K4me3 expression may be a predictive factor of poor prognosis in cancer (Li, Shen, and Chen 2018).