Epigenetics and cancer

Abstract

Epigenetic mechanisms act to change the accessibility of chromatin to transcriptional regulation locally and globally via modifications of the DNA and by modification or rearrangement of nucleosomes. Epigenetic gene regulation collaborates with genetic alterations in cancer development. This is evident from every aspect of tumor biology including cell growth and differentiation, cell cycle control, DNA repair, angiogenesis, migration, and evasion of host immunosurveillance. In contrast to genetic cancer causes, the possibility of reversing epigenetic codes may provide new targets for therapeutic intervention.Epigenetic programming is crucial in mammalian development, and stable inheritance of epigenetic settings is essential for the maintenance of tissue-and cell-typespecific functions (Li 2002). With the exception of controlled genomic rearrangements, such as those of the immunoglobulin and T-cell receptor genes in B and T cells, all other differentiation processes are initiated or maintained through epigenetic processes. Not surprisingly therefore, epigenetic gene regulation is characterized overall by a high degree of integrity and stability. Evidence is accumulating that suggests that the intrinsic stability is caused by multiple interlocking feedback mechanisms between functionally unrelated epigenetic layers, such as DNA methyltransferases (DNMTs) and histone modifying enzymes, resulting in the stable commitment of a locus to a particular activity state. In somatic cells, the transcriptional status of most genes is epigenetically fixed. However, other genes, such as cell cycle checkpoint genes and genes directly affected by exogenous stimuli such as growth factors or cell-cell contact, likely reside in a balanced state sensitive to dynamic adjustments in histone modifications, thereby allowing for rapid responses to specific stimuli. Perturbation of epigenetic balances may lead to alterations in gene expression, ultimately resulting in cellular transformation and malignant outgrowth; the involvement of deregulated epigenetic mechanisms in cancer development has received increased attention in recent years.Per definition, epigenetic regulators alter the activities and abilities of a cell without directly affecting and mutating the sequence of the DNA. In this review, we deal with epigenetic gene regulation as imposed by DNA methylation, covalent modifications of the canonical core histones, deposition of variant histone proteins, local nucleosome remodeling, and long-range epigenetic regulators. Understanding the molecular details behind "epigenetic cancer diseases" holds potentially important prospects for medical treatment, as it allows for novel strategies for drug development. A number of recent reviews have provided details on epigenetic mechanisms and their involvement in cancer, and we refer to these for more in-depth information on individual epigenetic mechanisms

DNA Methylation Suppresses Expression of the Urea Cycle Enzyme Carbamoyl Phosphate Synthetase 1 (CPS1) in Human Hepatocellular Carcinoma

“…DNA hypermethylation in promoter regions is associated with silencing of tumor suppressor genes because of direct or indirect prevention to accessing transcription factors in the promoter region. 22 Recent studies 21,23,24 have demonstrated that CpG island hypermethylation, via silencing of key cancer-related genes, plays a major causal role in cancer, including HCC.…”

Phenylbutyrate, a histone deacetylase inhibitor, protects against Adriamycin-induced cardiac injury

“…Acetylation homeostasis is a major epigenetic mechanism in cancer development and heart dysfunction [18][19][20], which is tightly regulated by the opposing histone acetyltransferases (HATs) and histone deacetylases (HDACs) [21,22]. Acetylation of histones opens chromatin structure for gene transcription; and acetylation also stabilizes and activates transcription factors for an increased activation of target genes [21].…”

Epigenetic changes in virus-associated human cancers

“…Within the last few years, a number of reviews with an emphasis on various aspects of epigenetic modifications in cancer have been published [11][12][13][14][15]. In this review, we will focus on hypermethylation and tumor suppressor gene silencing in cancer development, particularly in virus-associated cancers.…”