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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
For example, the nucleosome remodeling and histone deacetylase NuRD complex contain seven proteins that consists of HDAC1, HDAC2, RbAp46, RbAp48, Mi2, metastasis-associated protein 2 (MTA2) and methyl-CpG-binding domain protein 3 (MBD3) (Basta and Rauchman, 2015). Whereas MTA2 modulates the enzymatic activity of the histone deacetylase core complex, the MBD3 mediates the association of MTA2 with the core histone deacetylase complex. However, MBD3, although closely related to methylated DNA-binding MBD2 (methyl-CpG-binding domain protein 2), does not directly bind methylated DNA. MBD2 interacts with the NuRD complex and directs the complex to methylated DNA (Kupis et al., 2016). NuRD protein is known to silence the expression of genes through DNA methylation (Kupis et al., 2016). A separate study showed that the interaction between HDAC3 and silencing mediator for retinoid and thyroid hormone receptors/nuclear receptor co-repressor (SMRT/NCoR) stimulates HDAC3 enzyme, thereby reducing the expression of target genes (Guenther et al., 2001).
Epigenetic regulation of T cell development
Published in International Reviews of Immunology, 2023
Avik Dutta, Harini Venkataganesh, Paul E. Love
DNA methylation and demethylation have been shown to be key epigenetic events for proper thymocyte development [48–50]. One group showed that in the case of human αβ − T cell development, about 85% of DNA demethylation events that occur typically are associated with increased gene expression, reflecting how methylation of the promoter region of genes correlates with gene repression [50, 51]. They further showed a positive correlation of demethylation and increased expression of genes important for T cell development including RAG1, RAG2, CD8A, CD1A, PTCRA, OSBPL5, ZP1, CBFA2T3, AXIN2, ARPP21, BCL11B, RORC, RUNX3, CCR7, IKZF1 (IKAROS), and TCF7 [51]. Mbd2 (methyl-CpG-binding domain protein 2) is known as a “reader” of DNA methylation. Deletion of Mbd2 (germline deletion) resulted in a developmental block at the DN3 stage (Figure 2B) [52]. β-selection was severely affected with increased apoptosis and decreased proliferation of DN3 thymocytes [52]. It was also reported that WNT signaling was downregulated along with decreased expression of Tcf7 and c-Myc upon deletion of Mbd2 (Figure 2B) [52]. Further study is needed to decode how the change in methylation pattern due to loss of Mbd2 regulates expression of key genes.
Further understanding of epigenetic dysfunction of the retinal pigment epithelium in AMD
Published in Expert Review of Ophthalmology, 2020
Sonali Nashine, Maria Cristina Kenney
DNA MethylTransferases (DNMTs) maintain methylation patterns in the genome and are critical to cellular homeostasis. DNMT1 catalyzes the addition of methyl groups at CpG sites and is expressed in the retinal neurons [9]. DNMT1 is essential for the differentiation of RPE and photoreceptor cells and for maintaining the levels of retinoid-binding protein. DNMT1 deficiency leads to the loss of retinal neurons. DNMT3A and DNMT3B play a vital role in de novo methylation and their expression levels decrease as the retina ages. Loss of DNMT3B causes abnormal development of RPE and retina [10]. Other effectors of DNA methylation in mammalian cells include MAT1A (Methionine AdenosylTransferase 1 Alpha), MAT2B, MBD2 (Methyl-CpG Binding Domain protein 2), and MBD4. In our recent studies, the transmitochondrial AMD RPE cells showed reduced expression of DNMT1 and MBD2, whereas the expression levels of DNMT3A, DNMT3B, MAT1A, MAT2B, and MBD4 were upregulated compared to the normal RPE cybrid cells [11].
Early-life adversity-induced long-term epigenetic programming associated with early onset of chronic physical aggression: Studies in humans and animals
Published in The World Journal of Biological Psychiatry, 2019
Dimitry A. Chistiakov, Vladimir P. Chekhonin
Further studies showed that thyroid hormone and serotonin are the key mediators of the influence of maternal pup licking/grooming (LG) behaviour on hippocampal glucocorticoid receptor expression. Mother–pup interactions dynamically regulate association of Ngfi-a with the Nr3c1 promoter and Nr3c1expression (Hellstrom et al. 2012). Careful maternal care increases serotonin-dependent recruitment of Ngfi-a and its association with CBP and methyl-CpG binding domain protein-2 (MBD2), which in turn leads to increased histone acetylation, promoter demethylation and up-regulated hippocampal Nr3c1expression (Weaver et al. 2014).