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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
The associated G9a-based proteins, including GLP and EHMT1, whose gene locations are not found in the HLA/MHC locus, are able to form heterodimer in vivo along with G9a that is critically needed for H3K9me2-based methylation activity [92]. Any kind of genetic deletion associated with both of these proteins leads to a significant H3K9me2 reduction, representing that both protein subunits are very essential to enzyme-based activities [93]. Mutation at the active sites of the gene has shown to be found in in-vivo studies that indicated that HMNT activity plays an important role in H3K9me2 methylation [94]. However, global neuron analysis of gene expression in mice, along with specifically targeted deletions in the case of either GLP or G9a, identified the observable difference that might be created due to the differential subunit requirement in gene expression [95]. Furthermore, GLP loss is related to Kleefstra syndrome. This genetic disorder, found very rarely, is characterized by impairments in physical/social activities and intellectual disability [96]. No analysis has been done on the functional role of immune defense cells in this syndrome. Since GLP might display a specific potent role in gene regulation, it might be tested directly.
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
At E6.5 mouse pPGCs show histone marks similar to the surrounding somatic cells. Main changes in histone marks start at E7 with the decrease of H3K9me1 and H3K9me2 while H3K9me3 is retained at pericentric heterochromatin and it is followed by a significant increase of the repressive marks H3K27me3 and H2A/H4R3me2s at E8.25 (7,8) (Figure 4.6). PRDM1 and PRMD14 repress histone methyltransferase EHMT1, which participates in the methylation of H3K9. Meanwhile, the increase in the levels of H3K27me3 is probably due to EZH2 activity, an H3K27me3 methyltransferase, which is stably expressed in PGCs at E8.25 (7,8,52). Alternatively, this could be also the result of the observed downregulation of the H3K27me3 demethylases UTX and JMJD3 (53). Other repressive histone marks, such as H2A/H4R3me2s are conferred by PRMT5, a protein arginine methyltransferase that at E8.5 in PGC translocates to the nucleus to form a complex with PRDM1.
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].
Epigenetic regulation in Alzheimer’s disease: is it a potential therapeutic target?
Published in Expert Opinion on Therapeutic Targets, 2021
Following observations of increased histone methylation in the brain of 5xFAD mice and in postmortem AD brains [124], the same authors demonstrated that the treatment of 5xFAD mice with specific EHMT1/2 inhibitors reversed histone hyper-methylation and led to the recovery of glutamate receptor expression and excitatory synaptic function in prefrontal cortex and hippocampus [124]. Elevated levels of the histone methyltransferase EHMT1, which catalyzes H3K9me2, were also observed in Aβ-treated human stem cell-derived neurons, and selective EHMT1/2 inhibitors restored the glutamatergic synaptic transmission in these cells [159]. These studies have provided evidence that targeting histone tail methylation could represent a novel therapeutic approach in AD [124,159]. Indeed, a phase II clinical trial (NCT03867253) is currently ongoing to test the safety and preliminary efficacy of the new drug ORY-2001, a dual inhibitor of lysine-specific demethylase 1 (KDM1A) and monoamine oxidase B (MAO-B), in mild to moderate AD patients [158].
Inhibition of histone demethylase JMJD1C attenuates cardiac hypertrophy and fibrosis induced by angiotensin II
Published in Journal of Receptors and Signal Transduction, 2020
Shenqian Zhang, Ying Lu, Chenyang Jiang
A hallmark of pathological cardiac hypertrophy and fibrosis is the re-expression of fetal genes [2]. Epigenetic modifications are emerging regulators of this transcriptional reprograming [3–5]. Histone methylation is a conserved posttranslational modification, and regulates a multiple of genomic functions, including gene transcription [6]. Di- and tri-methylation of histone 3 lysine 9 (H3K9me2 and H3K9me3) are normally associated with transcriptional repressing and are silenced in hypertrophic and failing hearts in mouse and humans [7–9]. Histone methylation is dynamically controlled by lysine methyltransferases (KMTs) and lysine demethylases (KDMs). Zhang et al. reported that the H3K9me3 demethylase KDM4A/JMJD2A promoted pressure overload-induced LVH associated with activation of fetal genes re-expression [8]. Thienpont et al. reported that the H3K9me2 di-methyltransferase EHMT1/2 protected mice against pressure overload-induced LVH associated with activation of fetal genes re-expression [9]. Zhang et al. reported that the H3K9me2 demethylase KDM3A/JMJD1A promoted pressure overload-induced LVH associated with the activation of fetal genes re-expression [7]. Importantly, besides the H3K9me2/me1 demethylases JMJD1A, JMJD1C was also upregulated and positively associated with heart diseases [7,10,11]. However, its role in pathological heart diseases remains unknown.
A look into the use of Raman spectroscopy for brain and breast cancer diagnostics: linear and non-linear optics in cancer research as a gateway to tumor cell identity
Published in Expert Review of Molecular Diagnostics, 2020
Halina Abramczyk, Beata Brozek-Pluska, Arkadiusz Jarota, Jakub Surmacki, Anna Imiela, Monika Kopec
For example, in medulloblastoma, a series of rare focal copy-number alterations affecting histone-modifying genes, such as EHMT1, SMYD4, L3MBTL3, KDM4C (also known as JMJD2C) and KAT6A (also known as MYST3)37, were reported initially. Similarly, recurrent mutations in KMT2D (also known as MLL2), KMT2C (also known as MLL3), SMARCA4 and other genes were identified in MB tumors by gene re-sequencing [93].