Epigenomes — Open Access Epigenetics and Epigenomics Journal

Histone modifications regulate chromatin structure, gene transcription, and other nuclear processes. Among the histone modifications, methylation has been considered to be a stable, irreversible process due to the slow turnover of methyl groups in chromatin. However, the discovery of three different classes of lysine-specific demethylases—KDM1, Jumonji domain-containing demethylases, and lysyl oxidase-like 2 protein—has drastically changed this view, suggesting a role for dynamic histone methylation in different biological process. In this review, we describe the different mechanisms that these enzymes use to remove lysine histone methylation and discuss their role during physiological (cell differentiation) and pathological (carcinogenesis) processes. Full article

Skin cancer is one of the most common neoplasms worldwide, with a surprising tendency to increase its incidence. As with many cancer types nowadays, early diagnosis and proper management carries an excellent prognosis, up to 5-year survival rate of above 95% for most skin cancers, even though the long-term survival rate among metastatic melanoma patients remains only 5%. This review aims to summarize recent discoveries in epigenetic changes connected with cutaneous malignant melanoma (CMM), comprising of DNA methylation, histone modifications, miRNA regulation, nucleosome positioning and chromatin remodelling. Undoubtedly, personalised medicine based on both genetic and epigenetic changes of cancer is the future, the question remains: how long will it take to transport this treatment from the bench to the bedside? Full article

DNA hypomethylation at repetitive elements accounts for the genome-wide DNA hypomethylation common in cancer, including colorectal cancer (CRC). We identified a pericentromeric repeat element called SST1 frequently hypomethylated (>5% demethylation compared with matched normal tissue) in several cancers, including 28 of 128 (22%) CRCs. SST1 somatic demethylation associated with genome damage, especially in tumors with wild-type TP53. Seven percent of the 128 CRCs exhibited a higher (“severe”) level of demethylation (≥10%) that co-occurred with TP53 mutations. SST1 demethylation correlated with distinct histone marks in CRC cell lines and primary tumors: demethylated SST1 associated with high levels of the repressive histone 3 lysine 27 trimethylation (H3K27me3) mark and lower levels of histone 3 lysine 9 trimethylation (H3K9me3). Furthermore, induced demethylation of SST1 by 5-aza-dC led to increased H3K27me3 and reduced H3K9me3. Thus, in some CRCs, SST1 demethylation reflects an epigenetic reprogramming associated with changes in chromatin structure that may affect chromosomal integrity. The chromatin remodeler factor, the helicase lymphoid-specific (HELLS) enzyme, called the “epigenetic guardian of repetitive elements”, interacted with SST1 as shown by chromatin immunoprecipitation, and down-regulation of HELLS by shRNA resulted in demethylation of SST1 in vitro. Altogether these results suggest that HELLS contributes to SST1 methylation maintenance. Alterations in HELLS recruitment and function could contribute to the somatic demethylation of SST1 repeat elements undergone before and/or during CRC pathogenesis. Full article