Cancer is a major cause of death worldwide. Epigenetic changes in response to external (diet, sports activities, etc.) and internal events are increasingly implicated in tumor initiation and progression. In this review, we focused on post-translational changes in histones and, more particularly, the tri methylation of lysine from histone 3 (H3K27me3) mark, a repressive epigenetic mark often under- or overexpressed in a wide range of cancers. Two actors regulate H3K27 methylation: Jumonji Domain-Containing Protein 3 demethylase (JMJD3) and Enhancer of zeste homolog 2 (EZH2) methyltransferase. A number of studies have highlighted the deregulation of these actors, which is why this scientific review will focus on the role of JMJD3 and, consequently, H3K27me3 in cancer development. Data on JMJD3’s involvement in cancer are classified by cancer type: nervous system, prostate, blood, colorectal, breast, lung, liver, ovarian, and gastric cancers.
Background/Aim: In breast cancer, initiation of carcinogenesis leads to epigenetic dysregulation, which can lead for example to the loss of the heterochromatin skeleton SUV39H1/H3K9me3/HP1 or the supposed secondary skeleton TIP60/P400/H4K12ac/BRD (2/4), which allows the maintenance of chromatin integrity and plasticity. This study investigated the relationship between TIP60, P400 and H4K12ac and their implications in breast tumors. Materials and Methods: Seventy-seven patients diagnosed with breast cancer were included in this study. Chromatin immunoprecipitation (ChIP) assay was used to identify chromatin modifications. Western blot and reverse transcription and quantitative real-time PCR were used to determine protein and gene expression, respectively. Results: We verified the variation in H4K12ac enrichment and the colocalization of H4K12ac and TIP60 on the euchromatin and heterochromatin genes, respectively, by ChIP-qPCR and ChIP-reChIP, which showed an enrichment of H4K12ac on specific genes in tumors compared to the adjacent healthy tissue and a co-localization of H4K12ac with TIP60 in different breast tumor types. Furthermore, RNA and protein expression of TIP60 and P400 was investigated and overexpression of TIP60 and P400 mRNA was associated with tumor aggressiveness. Conclusion: There is a potential interaction between H4K12ac and TIP60 in heterochromatin or euchromatin in breast tumors. Breast cancer is the most frequent cancer (24.2% new cases in 2018) and the leading cause of cancer-related death (15% in 2018) (1). The majority of breast cancers are sporadic (non-hereditary), representing 80 to 90% of breast cancers (2). Deregulation of chromatin integrity and plasticity is among the causes of sporadic cancer (3). They occur at the epigenetic level in the different compartments of chromatin, which are heterochromatin (compacted chromatin) that inhibits gene expression, and euchromatin (relaxed chromatin) that promotes gene transcription. These chromatin states are maintained by so-called epigenetic proteins, which, by placing groups or marks on the histones, allow entry or exit from one state to another (4-6). Among these proteins, SUV39H1, which is a histone methyltransferase (HMT) that adds the H3K9me3 marker on the site where the HP1 protein will bind, thus forming the SUV39H1/H3K9me3/HP1 skeleton which keeps the chromatin closed and inhibits transcription in the heterochromatin region (7, 8). Heterochromatin houses inactive genes such as numerous oncogenes; the loss of this structure would lead to the transcription of oncogenes. Several studies have shown a loss of the SUV39H1 protein in cancer, but also a loss of the SUV39H1/H3K9me3/HP1 skeleton during the onset of carcinogenesis (7, 9). The acetyl-transferases (HAT) such as TIP60 are able to add acetyl groups on the N-terminal tails of histones resulting in the opening of the chromatin leading to euchromatin (10). TIP60 is also capable of acetylating non-histone proteins such as p53 and ATM allowing their activation (11-13). Many studies have s...
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