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Abstract: In addition to genetic events, a variety of epigenetic events have been widely reported to contribute to the onset of many diseases including cancer. DNA methylation and histone modifications (such as acetylation, methylation, sumoylation, and phosphorylation) involving chromatin remodelling are among the most studied epigenetic mechanisms for regulation of gene expression leading, when altered, to some diseases. Epigenetic therapy tries to reverse the aberrations followed to the disruption of the balance of the epigenetic signalling ways through the use of both natural compounds and synthetic molecules, active on specific epi-targets. Such epi-drugs are, for example, inhibitors of DNA methyltransferases, histone deacetylases, histone acetyltransferases, histone methyltransferases, and histone demethylases. In this review we will focus on the chemical aspects of such molecules, joined to their effective (or potential) application in cancer therapy. [Copyright &y& Elsevier]

Abstract: Recent successes of therapeutic intervention in chronic inflammatory diseases using epigenetic modifiers such as histone deacetylase inhibitors and inhibitors of DNA methylation suggest that epigenetic reprogramming plays a role in the aetiology of these diseases. The epigenetic signature of a given immune cell is reflected in the history of modifications from different signals the cell has been subjected to during differentiation. Like other cells, differentiating immune cells are dependent on a complex combination of inter- and intracell signalling as well as transcription machineries to modulate their epigenomes in order to mediate differentiation. Despite extensive research into these processes, the link between cellular signalling and epigenetic modulation remains poorly understood. Here, we review recent progress and discuss key factors driving epigenetic modulation in chronic inflammation. [Copyright &y& Elsevier]

Abstract: Our current knowledge of the deregulation that occurs during the onset and progression of cancer and other diseases leads us to recognize both genetic and epigenetic alterations as being at the core of the pathological state. The epigenetic landscape includes a variety of covalent modifications that affect the methylation status of DNA but also the post-translational modifications of histones, and determines the structural features of chromatin that ultimately control the transcriptional outcome of the cell to accommodate developmental, proliferative or environmental requirements. MicroRNAs are small non-coding RNAs that regulate the expression of complementary messenger RNAs and function as key controllers in a myriad of cellular processes, including proliferation, differentiation and apoptosis. In the last few years, increasing evidence has indicated that a substantial number of microRNA genes are subjected to epigenetic alterations, resulting in aberrant patterns of expression upon the occurrence of cancer. In this review we discuss microRNA genes that are epigenetically modified in cancer cells, and the role that microRNAs themselves can have as chromatin modifiers. [Copyright &y& Elsevier]

Abstract: DNA methylation is an important and reversible epigenetic modification, which regulates genomic stability and cellular plasticity. Faithful DNA methylation is essential for mammalian development and health, and perturbation of methylation dynamics contributes to the development of disease, including cancer. The discovery and validation of the biological indicators (biomarkers) for human cancers are essential steps in the development of methods for accurate subtype classification and outcome prediction in clinic oncology. While genetics (SNP, LOH and mutation) and expression profiling (mRNA and protein) of biomarkers have been extensively assessed for cancer diagnosis and prognosis, the potential for using epigenetic fingerprints for early diagnosis and outcome prediction in clinic oncology propels the exploration of using DNA methylation as a biomarker for cancer prognosis. Both the promises and challenges to realizing the clinical utility of the DNA methylation in cancer management are discussed in this review. [Copyright &y& Elsevier]

Abstract: DNA methylation, post-translational modifications of histones and high order organization of chromatin in cell nuclei are the components of the epigenome. Epigenetic regulation of gene expression is specific for each cell type, within different tissues, according to stages of development and (in the adult organism) of differentiation. Almost invariably, this regulation is altered in disease states, including cancer. The complete understanding of the identity of the epigenome of cancer has been so far hampered, due to the technical limitations and costs of the genome-wide analyses required. The recent development of next generation sequencing (NGS) technologies, however, holds the promise of fast, reliable and cost-effective analyses. Here we review the main approaches employed thus far to identify altered epigenetic patterns in cancer cells, and analyse how they are predicted to evolve in the scenario of the ultra high-throughput (UHT) screenings. [Copyright &y& Elsevier]

Abstract: Epigenetic refers to a range of heritable chromatin modifications including DNA methylation, histone modifications, remodeling of nucleosomes and higher order chromatin modifications. In the framework of chromatin remodeling activities, the poly(ADP-ribosyl)ation of nuclear proteins catalyzed by PARPs, particularly PARP-1 and PARP-2, plays a fundamental role and as such have the potential to orchestrate various chromatin-based biological tasks including transcription, DNA repair and differentiation. In this review, we propose a short overview of the more recent experimental data that shed light on the role of poly(ADP-ribosyl)ation in the translation of the histone code. We will essentially focus on the different mechanisms by which PARP activity regulates the global chromatin environment and how this affects cellular pathways. [Copyright &y& Elsevier]

Abstract: HIC1 (Hypermethylated in Cancer 1), as it name implied, was originally isolated as a new candidate tumor suppressor gene located at 17p13.3 because it resides in a CpG island that is hypermethylated in many types of human cancers. HIC1 encodes a transcription factor associating an N-terminal BTB/POZ domain to five C-terminal Krüppel-like C2H2 zinc finger motifs. In this review, we will begin by providing an overview of the current knowledge on HIC1 function, mainly gained from in vitro studies, as a sequence-specific transcriptional repressor interacting with a still growing range of HDAC-dependent and HDAC-independent corepressor complexes. We will then summarize the studies that have demonstrated frequent hypermethylation changes or losses of heterozygosity of the HIC1 locus in human cancers. Next, we will review animal models which have firmly established HIC1 as a bona fide tumor suppressor gene epigenetically silenced and functionally cooperating notably with p53 within a complex HIC1-p53-SIRT1 regulatory loop. Finally, we will discuss how this epigenetic inactivation of HIC1 might “addict” cancer cells to altered survival and signaling pathways or to lineage-specific transcription factors during the early stages of tumorigenesis. [Copyright &y& Elsevier]