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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
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.
Genetic polymorphisms of PPAR genes and human cancers: evidence for gene–environment interactions
Published in Journal of Environmental Science and Health, Part C, 2019
In summary, although the PPAR-β/δ-null mouse model showed strong in vivo evidence of a role of PPAR receptors in development and cell proliferation,44 however, so far, studies that convincingly proved a clear association between exposure to PPAR ligands and carcinogenicity are still inconclusive, particularly in humans. It is important to consider that a ligand that activates a PPAR, may at the same time cause toxicity through other mechanisms of action. Ligand-induced toxicity may take place by receptor-independent events, or by both PPAR-dependent and PPAR-independent mechanisms.45 Additionally, if/when a PPAR mediates an adverse effect, genetic polymorphisms of that PPAR need to be examined as they may be significant effect modifiers. Further, like most transcription factors, PPARs may be influenced by epigenetic regulators, which may modify ligand-mediated transcription and gene expression pathways. Epigenetic mechanisms, such as histone acetylation, DNA methylation, and miRNAs, may promote or inhibit the transcription of various PPARs by governing their mRNA translation or breakdown. Recently, a zinc-finger protein was identified among a group of unidentified transcription factors bound to the PPAR-γ gene non-methylated promoter.46 Following an unknown trigger, the promoter gets hypermethylated, enriched in H3K9me2 & 3, and H3K27me3, then followed by binding a repressive complex, including DNMT2b, HDAC1, EZH2, and other components, ultimately resulting in repression of transcription. In addition, posttranslational modifications (such as phosphorylation and ubiquitination), interactions with coactivators -such as PPARGCA, CBP-p300, and SCRC1- and corepressors -such as RIP140α, SMRTα- may also affect the transcriptional activity and stability of PPARs.47 So far, very few studies have examined the contribution of these mechanisms to PPAR-mediated cancer risk.