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Medulloblastoma
Published in Dongyou Liu, Tumors and Cancers, 2017
Across all medulloblastoma subsets, frequent genetic alterations relate to chromatin regulators (e.g., MLL2, MLL3, and EHMT1; KDM6A, KDM6B, JMJD2C, and JMJD2B; and SMARCA4, CHD7, and ARID1B) and methylation patterns at and downstream of promoters (e.g., hypomethylation and overexpresssion of the mRNA processing gene LIN28B in most Group 3 and Group 4 tumors [2].
Vitamin C and Somatic Cell Reprogramming
Published in Qi Chen, Margreet C.M. Vissers, Cancer and Vitamin C, 2020
Neural stem/precursor cells (NSCs) are considered a potential cell source for the treatment of Parkinson disease (PD), which is characterized by the progressive degeneration of dopamine (DA) neurons in the midbrain [78]. Fibroblast-derived iPSCs can be efficiently differentiated into NSCs, giving rise to neuronal and glial cell types in culture that were shown to improve the clinical symptoms of a rat model of Parkinson disease [79]. Similar to the initial rationale for adding vitamin C to somatic cells during reprogramming, several antioxidants were tested in an attempt to mitigate the effect of cellular aging and senescence potentially caused by ROS generation in NSC cultures [80]. Compared to numerous antioxidants tested, only vitamin C treatment protected in vitro–expanded NSCs from losing DA neurogenic potential, and transplantation of vitamin C–treated NSCs resulted in improved behavioral restoration, along with enriched DA neuron engraftment in a rat model of PD [80]. The effect on NSC function was attributed to the role of vitamin C as a regulator of DNA demethylation rather than its antioxidant function, and the faithful expression of midbrain-specific markers in engrafted neurons [80]. Another study also described the role of vitamin C in enhancing NSC differentiation toward DA neurons through boosting of Tet1 and Jmjd3 (KDM6B) activity [81]. Treatment with vitamin C may therefore be important for the maintenance of an epigenetic state that favors enhanced survival of cultured NSCs primed for DA neuron differentiation and may improve the efficacy of stem cell therapies generated from iPSCs for the treatment of PD.
Epigenetic regulation of T cell development
Published in International Reviews of Immunology, 2023
Avik Dutta, Harini Venkataganesh, Paul E. Love
Several reports suggest that polycomb group (PcG) proteins govern the H3K27 methylation mark [25] and that Polycomb repressor complex (PRC) maintains the repressive state. There are three groups of PRCs: PRC1, PRC2, and Polycomb Repressive-Deubiquitinase (PR-DUB) complex [26, 27]. Each group has individual ways of remodeling chromatin, contributing to the epigenetic repression of genes important for cell development and proliferation. The PRC1 complex, which consists of several proteins including BMI-1, Ring1, and HPH proteins, recognizes and trimethylates K27 of histone 3 (H3K27me3) and helps to maintain the repressive state. The PRC2 complex includes EZH1 (enhancer of zeste homolog 1), EZH2, EED and SUV12 and initiates early gene repression with the help of histone deacetylases (HDACs) and DNMTs [25]. The discovery of histone demethylase LSD1 (Lysine-specific histone demethylase 1 A; encoded by the KDM1A gene) advanced the field as previously it was thought that histone methylation is permanent. This discovery has contributed to a dynamic view of chromatin remodeling [23, 28]. LSD1 demethylates H3K4 and H3K9 and is found to be upregulated in many cancers including T cell acute lymphoblastic leukemia (T-ALL) [29]. Several reports have also shown that the histone H3 K27 demethylases, KDM6A (Utx) and KDM6B (Jmjd3), help to shape the chromatin architecture and regulate gene expression by removing repressive histone modifications [30].
Specific low-frequency electromagnetic fields induce expression of active KDM6B associated with functional changes in U937 cells
Published in Electromagnetic Biology and Medicine, 2020
Giulia Pinton, Angelo Ferraro, Massimo Balma, Laura Moro
KDM6B, also known as JMJD3, is a chromatin remodeling factor which specifically demethylates di- or tri-methylated lysine 27 of histone H3 (H3K27me2 or H3K27me3), affecting gene expression (Burchfield et al. 2015; Manente et al. 2016; Swigut and Wysocka 2007). Post-translational modifications of histone tails, and in particular methylation, deeply affect the overall chromatin structure during crucial cellular processes. Indeed, H3K27me3 is enriched in highly condensed and thereby inactive chromatin, whereas loss of H3K27me3 is linked with transcriptionally active genes (Bernstein et al. 2006; Dong and Weng 2013; Salminen et al. 2014). The action of KDM6B is counteracted by EZH2, the catalytic subunit of the polycomb repressor complex 2 (PRC2), whose primary function is to add methyl groups at lysine 27 on histone H3 by using the cofactor S-adenosyl-L-methionine (SAM) (Cao et al. 2002).
The diagnostic performance of lysine(K)-specific demethylase 6B (KDM6B) in non-small cell lung cancer
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Ting Ge, Ying Zhou, Hongmin Lu
Histone methylation plays a key role in the regulation of gene expression during the cell cycle and its abnormality may be related to tumor occurrence [21]. It was reported that site-specific histone methyltransferases and demethylases could regulate histone methylation, which is a reversible process [22]. Abnormal expression or mutation of histone methyltransferases and demethylases related genes were frequently associated with cancer progression [23]. KDM6B encoding an enzyme which can catalyze histone H3K27me3 demethylation. Abnormal H3K27me3 methylation was reported to be correlated with several cancers, including melanoma, colon, gastric, stomach, ovarian, breast and kidney cancers [24,25]. Thus, KDM6B may also involve in tumor progression.