'; ?> geneimprint : Hot off the Press http://www.geneimprint.com/site/hot-off-the-press Daily listing of the most recent articles in epigenetics and imprinting, collected from the PubMed database. en-us Tue, 26 May 2015 08:45:27 PDT Tue, 26 May 2015 08:45:27 PDT jirtle@radonc.duke.edu james001@jirtle.com Long noncoding RNAs: Lessons from Genomic imprinting. Kanduri C
Biochim Biophys Acta (May 2015)

Genomic imprinting has been a great resource for studying transcriptional and post-transcriptional-based gene regulation by long noncoding RNAs (lncRNAs). In this article, I overview the functional role of intergenic lncRNAs (H19, IPW and MEG3), antisense lncRNAs (Kcnq1ot1, Airn, Nespas, Ube3a-ATS) and enhancer lncRNAs (IG-DMR eRNAs) to understand the diverse mechanisms being employed by them in cis and/or trans to regulate the parent-of-origin-specific expression of target genes. Recent evidence suggests that some of the lncRNAs regulate imprinting by promoting intra-chromosomal higher order chromatin compartmentalisation, affecting replication timing and sub-nuclear positioning. Whereas others act via transcriptional occlusion or transcriptional collision-based mechanisms. By establishing genomic imprinting of target genes, the lncRNAs play a critical role in important biological functions, such as placental and embryonic growth, pluripotency maintenance, cell differentiation and neural related functions such as synaptic development and plasticity. An emerging consensus from the recent evidence is that the imprinted lncRNAs fine-tune gene expression of the protein coding genes to maintain their dosage in cell. Hence lncRNAs from imprinted clusters offer insights into their mode of action and these mechanisms have been the basis for uncovering the mode of action of lncRNAs in several other biological contexts. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1.]]>
Mon, 25 May 2015 00:00:00 PDT
Array-based DNA-methylation analysis in individuals with developmental delay/intellectual disability and normal molecular karyotype. Kolarova J, Tangen I, Bens S, Gillessen-Kaesbach G, Gutwein J, Kautza M, Rydzanicz M, Stephani U, Siebert R, Ammerpohl O, Caliebe A
Eur J Med Genet (May 2015)

Despite recent progresses in molecular karyotyping and clinical sequencing the cause of intellectual disability in a considerable subset of individuals affected by this phenotype remains elusive. As intellectual disability is also a feature of various imprinting disorders and some monogenic forms of intellectual disability are caused by epigenetic modifiers we hypothesized that changes in DNA-methylation might be associated with or even causative in some cases of intellectual disability. Therefore, we performed a DNA-methylation analysis of peripheral blood samples from 82 patients with intellectual disability and additional features using the HumanMethylation450k BeadChip. The findings were compared to that of 19 normal controls. Differentially methylated loci were validated by bisulfite pyrosequencing. On a global level, we failed to detect a robust DNA-methylation signature segregating individuals with intellectual disability from controls. Using an individual approach, we identified 157 regions showing individual DNA-methylation changes in at least one patient. These correlated to 107 genes including genes linked to conditions associated with intellectual disability, namely COLEC11, SHANK2, GLI2 and KCNQ2, as well as imprinted genes like FAM50B and MEG3. The latter was suggestive of an undiagnosed Temple syndrome which could be confirmed by diagnostic tests. Subsequent in-depth analysis of imprinted loci revealed DNA-methylation changes at additional imprinted loci, i.e. PPIEL, IGF2R, MEG8 and MCTS2/HM13, in up to four patients. Our findings indicate that imprinting disorders are rare but probably under-diagnosed in patients with intellectual disability and moreover point to DNA-methylation changes as potential alternative means to identify deregulated genes involved in the pathogenesis of intellectual disability.]]>
Sun, 24 May 2015 00:00:00 PDT
Genomic Imprinting: A Missing Piece of the Multiple Sclerosis Puzzle? Ruhrmann S, Stridh P, Kular L, Jagodic M
Int J Biochem Cell Biol (May 2015)

Evidence for parent-of-origin effects in complex diseases such as Multiple Sclerosis (MS) strongly suggests a role for epigenetic mechanisms in their pathogenesis. In this review we describe the importance of accounting for parent-of-origin when identifying new risk variants for complex diseases and discuss how genomic imprinting, one of the best-characterized epigenetic mechanisms causing parent-of-origin effects, may impact etiology of complex diseases. While the role of imprinted genes in growth and development is well established, the contribution and molecular mechanisms underlying the impact of genomic imprinting in immune functions and inflammatory diseases are still largely unknown. Here we discuss emerging roles of imprinted genes in regulation of inflammatory responses with a particular focus on the Dlk1 cluster that has been implicated in etiology of experimental MS-like disease and Type 1 Diabetes. Moreover, we speculate on the potential wider impact of imprinting via the action of imprinted microRNAs, which are abundantly present in the Dlk1 locus and predicted to fine-tune important immune functions. Finally, we reflect on how unrelated imprinted genes or imprinted genes together with non-imprinted genes can interact in so-called imprinted gene networks (IGN) and suggest that IGNs could partly explain observed parent-of-origin effects in complex diseases. Unveiling the mechanisms of parent-of-origin effects is therefore likely to teach us not only about the etiology of complex diseases but also about the unknown roles of this fascinating phenomenon underlying uneven genetic contribution from our parents.]]>
Sat, 23 May 2015 00:00:00 PDT
Identification of diagnostic markers in colorectal cancer via integrative epigenomics and genomics data. Kok-Sin T, Mokhtar NM, Ali Hassan NZ, Sagap I, Mohamed Rose I, Harun R, Jamal R
Oncol Rep (May 2015)

Apart from genetic mutations, epigenetic alteration is a common phenomenon that contributes to neoplastic transformation in colorectal cancer. Transcriptional silencing of tumor‑suppressor genes without changes in the DNA sequence is explained by the existence of promoter hypermethylation. To test this hypothesis, we integrated the epigenome and transcriptome data from a similar set of colorectal tissue samples. Methylation profiling was performed using the Illumina InfiniumHumanMethylation27 BeadChip on 55 paired cancer and adjacent normal epithelial cells. Fifteen of the 55 paired tissues were used for gene expression profiling using the Affymetrix GeneChip Human Gene 1.0 ST array. Validation was carried out on 150 colorectal tissues using the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) technique. PCA and supervised hierarchical clustering in the two microarray datasets showed good separation between cancer and normal samples. Significant genes from the two analyses were obtained based on a ≥2‑fold change and a false discovery rate (FDR) p-value of <0.05. We identified 1,081 differentially hypermethylated CpG sites and 36 hypomethylated CpG sites. We also found 709 upregulated and 699 downregulated genes from the gene expression profiling. A comparison of the two datasets revealed 32 overlapping genes with 27 being hypermethylated with downregulated expression and 4 hypermethylated with upregulated expression. One gene was found to be hypomethylated and downregulated. The most enriched molecular pathway identified was cell adhesion molecules that involved 4 overlapped genes, JAM2, NCAM1, ITGA8 and CNTN1. In the present study, we successfully identified a group of genes that showed methylation and gene expression changes in well-defined colorectal cancer tissues with high purity. The integrated analysis gives additional insight regarding the regulation of colorectal cancer-associated genes and their underlying mechanisms that contribute to colorectal carcinogenesis.]]>
Fri, 22 May 2015 00:00:00 PDT
Endothelial epigenetics in biomechanical stress: disturbed flow-mediated epigenomic plasticity in vivo and in vitro. Jiang YZ, Manduchi E, Jiménez JM, Davies PF
Arterioscler Thromb Vasc Biol (Jun 2015)

Arterial endothelial phenotype is regulated by local hemodynamic forces that are linked to regional susceptibility to atherogenesis. A complex hierarchy of transcriptional, translational, and post-translational mechanisms is greatly influenced by the characteristics of local arterial shear stress environments. We discuss the emerging role of localized disturbed blood flow on epigenetic mechanisms of endothelial responses to biomechanical stress, including transcriptional regulation by proximal promoter DNA methylation, and post-transcriptional and translational regulation of gene and protein expression by chromatin remodeling and noncoding RNA-based mechanisms. Dynamic responses to flow characteristics in vivo and in vitro include site-specific differentially methylated regions of swine and mouse endothelial methylomes, histone marks regulating chromatin conformation, microRNAs, and long noncoding RNAs. Flow-mediated epigenomic responses intersect with cis and trans factor regulation to maintain endothelial function in a shear-stressed environment and may contribute to localized endothelial dysfunctions that promote atherosusceptibility.]]>
Thu, 21 May 2015 00:00:00 PDT
DNA methylation and epigenomics: new technologies and emerging concepts. Chatterjee A, Eccles MR
Genome Biol (2015)

A report of the Keystone Symposia joint meetings on DNA Methylation and Epigenomics held in Keystone, Colorado, USA, 29 March to 3 April, 2015.]]>
Wed, 20 May 2015 00:00:00 PDT
Recent developments in epigenetics of acute and chronic kidney diseases. Reddy MA, Natarajan R
Kidney Int (May 2015)

The growing epidemic of obesity and diabetes, the aging population as well as prevalence of drug abuse has led to significant increases in the rates of the closely associated acute and chronic kidney diseases, including diabetic nephropathy. Furthermore, evidence shows that parental behavior and diet can affect the phenotype of subsequent generations via epigenetic transmission mechanisms. These data suggest a strong influence of the environment on disease susceptibility and that, apart from genetic susceptibility, epigenetic mechanisms need to be evaluated to gain critical new information about kidney diseases. Epigenetics is the study of processes that control gene expression and phenotype without alterations in the underlying DNA sequence. Epigenetic modifications, including cytosine DNA methylation and covalent post-translational modifications of histones in chromatin, are part of the epigenome, the interface between the stable genome and the variable environment. This dynamic epigenetic layer responds to external environmental cues to influence the expression of genes associated with disease states. The field of epigenetics has seen remarkable growth in the past few years with significant advances in basic biology, contributions to human disease, as well as epigenomics technologies. Further understanding of how the renal cell epigenome is altered by metabolic and other stimuli can yield novel new insights into the pathogenesis of kidney diseases. In this review, we have discussed the current knowledge on the role of epigenetic mechanisms (primarily DNAme and histone modifications) in acute and chronic kidney diseases, and their translational potential to identify much needed new therapies.Kidney International advance online publication, 20 May 2015; doi:10.1038/ki.2015.148.]]>
Wed, 20 May 2015 00:00:00 PDT
Current trend of annotating single nucleotide variation in humans - A case study on SNVrap. Li MJ, Wang J
Methods (Jun 2015)

As high throughput methods, such as whole genome genotyping arrays, whole exome sequencing (WES) and whole genome sequencing (WGS), have detected huge amounts of genetic variants associated with human diseases, function annotation of these variants is an indispensable step in understanding disease etiology. Large-scale functional genomics projects, such as The ENCODE Project and Roadmap Epigenomics Project, provide genome-wide profiling of functional elements across different human cell types and tissues. With the urgent demands for identification of disease-causal variants, comprehensive and easy-to-use annotation tool is highly in demand. Here we review and discuss current progress and trend of the variant annotation field. Furthermore, we introduce a comprehensive web portal for annotating human genetic variants. We use gene-based features and the latest functional genomics datasets to annotate single nucleotide variation (SNVs) in human, at whole genome scale. We further apply several function prediction algorithms to annotate SNVs that might affect different biological processes, including transcriptional gene regulation, alternative splicing, post-transcriptional regulation, translation and post-translational modifications. The SNVrap web portal is freely available at http://jjwanglab.org/snvrap.]]>
Mon, 18 May 2015 00:00:00 PDT
Aberrant methylation of imprinted genes is associated with negative hormone receptor status in invasive breast cancer. Barrow TM, Barault L, Ellsworth RE, Harris HR, Binder AM, Valente AL, Shriver CD, Michels KB
Int J Cancer (Aug 2015)

Epigenetic regulation of imprinted genes enables monoallelic expression according to parental origin, and its disruption is implicated in many cancers and developmental disorders. The expression of hormone receptors is significant in breast cancer because they are indicators of cancer cell growth rate and determine response to endocrine therapies. We investigated the frequency of aberrant events and variation in DNA methylation at nine imprinted sites in invasive breast cancer and examined the association with estrogen and progesterone receptor status. Breast tissue and blood from patients with invasive breast cancer (n = 38) and benign breast disease (n = 30) were compared with those from healthy individuals (n = 36), matched with the cancer patients by age at diagnosis, ethnicity, body mass index, menopausal status and familial history of cancer. DNA methylation and allele-specific expression were analyzed by pyrosequencing. Tumor-specific methylation changes at IGF2 DMR2 were observed in 59% of cancer patients, IGF2 DMR0 in 38%, DIRAS3 DMR in 36%, GRB10 ICR in 23%, PEG3 DMR in 21%, MEST ICR in 19%, H19 ICR in 18%, KvDMR in 8% and SNRPN/SNURF ICR in 4%. Variation in methylation was significantly greater in breast tissue from cancer patients compared with that in healthy individuals and benign breast disease. Aberrant methylation of three or more sites was significantly associated with negative estrogen-alpha (Fisher's exact test, p = 0.02) and progesterone-A (p = 0.02) receptor status. Aberrant events and increased variation in imprinted gene DNA methylation, therefore, seem to be frequent in invasive breast cancer and are associated with negative estrogen and progesterone receptor status, without loss of monoallelic expression.]]>
Mon, 18 May 2015 00:00:00 PDT
Pyrosequencing for accurate imprinted allele expression analysis. Yang B, Damaschke N, Yao T, McCormick J, Wagner J, Jarrard D
J Cell Biochem (Jul 2015)

Genomic imprinting is an epigenetic mechanism that restricts gene expression to one inherited allele. Improper maintenance of imprinting has been implicated in a number of human diseases and developmental syndromes. Assays are needed that can quantify the contribution of each paternal allele to a gene expression profile. We have developed a rapid, sensitive quantitative assay for the measurement of individual allelic ratios termed Pyrosequencing for Imprinted Expression (PIE). Advantages of PIE over other approaches include shorter experimental time, decreased labor, avoiding the need for restriction endonuclease enzymes at polymorphic sites, and prevent heteroduplex formation which is problematic in quantitative PCR-based methods. We demonstrate the improved sensitivity of PIE including the ability to detect differences in allelic expression down to 1%. The assay is capable of measuring genomic heterozygosity as well as imprinting in a single run. PIE is applied to determine the status of Insulin-like Growth Factor-2 (IGF2) imprinting in human and mouse tissues. J. Cell. Biochem. 116: 1165-1170, 2015. © 2015 Wiley Periodicals, Inc.]]>
Wed, 13 May 2015 00:00:00 PDT
Proceedings of the second international molecular pathological epidemiology (MPE) meeting. Ogino S, Campbell PT, Nishihara R, Phipps AI, Beck AH, Sherman ME, Chan AT, Troester MA, Bass AJ, Fitzgerald KC, Irizarry RA, Kelsey KT, Nan H, Peters U, Poole EM, Qian ZR, Tamimi RM, Tchetgen Tchetgen EJ, Tworoger SS, Zhang X, Giovannucci EL, van den Brandt PA, Rosner BA, Wang M, Chatterjee N, Begg CB
Cancer Causes Control (May 2015)

Disease classification system increasingly incorporates information on pathogenic mechanisms to predict clinical outcomes and response to therapy and intervention. Technological advancements to interrogate omics (genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics, interactomics, etc.) provide widely open opportunities in population-based research. Molecular pathological epidemiology (MPE) represents integrative science of molecular pathology and epidemiology. This unified paradigm requires multidisciplinary collaboration between pathology, epidemiology, biostatistics, bioinformatics, and computational biology. Integration of these fields enables better understanding of etiologic heterogeneity, disease continuum, causal inference, and the impact of environment, diet, lifestyle, host factors (including genetics and immunity), and their interactions on disease evolution. Hence, the Second International MPE Meeting was held in Boston in December 2014, with aims to: (1) develop conceptual and practical frameworks; (2) cultivate and expand opportunities; (3) address challenges; and (4) initiate the effort of specifying guidelines for MPE. The meeting mainly consisted of presentations of method developments and recent data in various malignant neoplasms and tumors (breast, prostate, ovarian and colorectal cancers, renal cell carcinoma, lymphoma, and leukemia), followed by open discussion sessions on challenges and future plans. In particular, we recognized need for efforts to further develop statistical methodologies. This meeting provided an unprecedented opportunity for interdisciplinary collaboration, consistent with the purposes of the Big Data to Knowledge, Genetic Associations and Mechanisms in Oncology, and Precision Medicine Initiative of the US National Institute of Health. The MPE meeting series can help advance transdisciplinary population science and optimize training and education systems for twenty-first century medicine and public health.]]>
Sat, 09 May 2015 00:00:00 PDT
Proteogenomics of the human hippocampus: The road ahead. Kang MG, Byun K, Kim JH, Park NH, Heinsen H, Ravid R, Steinbusch HW, Lee B, Park YM
Biochim Biophys Acta (Jul 2015)

The hippocampus is one of the most essential components of the human brain and plays an important role in learning and memory. The hippocampus has drawn great attention from scientists and clinicians due to its clinical importance in diseases such as Alzheimer's disease (AD), non-AD dementia, and epilepsy. Understanding the function of the hippocampus and related disease mechanisms requires comprehensive knowledge of the orchestration of the genome, epigenome, transcriptome, proteome, and post-translational modifications (PTMs) of proteins. The past decade has seen remarkable advances in the high-throughput sequencing techniques that are collectively called next generation sequencing (NGS). NGS enables the precise analysis of gene expression profiles in cells and tissues, allowing powerful and more feasible integration of expression data from the gene level to the protein level, even allowing "-omic" level assessment of PTMs. In addition, improved bioinformatics algorithms coupled with NGS technology are finally opening a new era for scientists to discover previously unidentified and elusive proteins. In the present review, we will focus mainly on the proteomics of the human hippocampus with an emphasis on the integrated analysis of genomics, epigenomics, transcriptomics, and proteomics. Finally, we will discuss our perspectives on the potential and future of proteomics in the field of hippocampal biology. This article is part of a Special Issue entitled: Neuroproteomics: Applications in Neuroscience and Neurology.]]>
Sat, 09 May 2015 00:00:00 PDT
The landscape of genomic imprinting across diverse adult human tissues. Baran Y, Subramaniam M, Biton A, Tukiainen T, Tsang EK, Rivas MA, Pirinen M, Gutierrez-Arcelus M, Smith KS, Kukurba KR, Zhang R, Eng C, Torgerson DG, Urbanek C,  , Li JB, Rodriguez-Santana JR, Burchard EG, Seibold MA, MacArthur DG, Montgomery SB, Zaitlen NA, Lappalainen T
Genome Res (May 2015)

Genomic imprinting is an important regulatory mechanism that silences one of the parental copies of a gene. To systematically characterize this phenomenon, we analyze tissue-specificity of imprinting from allelic expression data in 1582 primary tissue samples from 178 individuals from the Genotype Tissue Expression (GTEx) project. We characterize imprinting in 42 genes, including both novel and previously identified genes. Tissue-specificity of imprinting is widespread, and gender-specific effects are revealed in a small number of genes in muscle with stronger imprinting in males. IGF2 shows maternal expression in the brain instead of the canonical paternal expression elsewhere. Imprinting appears to have only a subtle impact on tissue-specific expression levels, with genes lacking a systematic expression difference between tissues with imprinted and biallelic expression. In summary, our systematic characterization of imprinting in adult tissues highlights variation in imprinting between genes, individuals, and tissues.]]>
Fri, 08 May 2015 00:00:00 PDT
Epigenome maps offer clues to disease origins.
Cancer Discov (May 2015)

The Roadmap Epigenomics Program has published the first comprehensive maps and analyses of human epigenomes across more than 100 tissues and cell types, providing a window into the links between DNA and disease. One study using data from the program found that it's possible to pinpoint where a cancer originated by examining the distribution of mutations along its genome.]]>
Tue, 05 May 2015 00:00:00 PDT
Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research. Maes M, Nowak G, Caso JR, Leza JC, Song C, Kubera M, Klein H, Galecki P, Noto C, Glaab E, Balling R, Berk M
Mol Neurobiol (May 2015)

Meta-analyses confirm that depression is accompanied by signs of inflammation including increased levels of acute phase proteins, e.g., C-reactive protein, and pro-inflammatory cytokines, e.g., interleukin-6. Supporting the translational significance of this, a meta-analysis showed that anti-inflammatory drugs may have antidepressant effects. Here, we argue that inflammation and depression research needs to get onto a new track. Firstly, the choice of inflammatory biomarkers in depression research was often too selective and did not consider the broader pathways. Secondly, although mild inflammatory responses are present in depression, other immune-related pathways cannot be disregarded as new drug targets, e.g., activation of cell-mediated immunity, oxidative and nitrosative stress (O&NS) pathways, autoimmune responses, bacterial translocation, and activation of the toll-like receptor and neuroprogressive pathways. Thirdly, anti-inflammatory treatments are sometimes used without full understanding of their effects on the broader pathways underpinning depression. Since many of the activated immune-inflammatory pathways in depression actually confer protection against an overzealous inflammatory response, targeting these pathways may result in unpredictable and unwanted results. Furthermore, this paper discusses the required improvements in research strategy, i.e., path and drug discovery processes, omics-based techniques, and systems biomedicine methodologies. Firstly, novel methods should be employed to examine the intracellular networks that control and modulate the immune, O&NS and neuroprogressive pathways using omics-based assays, including genomics, transcriptomics, proteomics, metabolomics, epigenomics, immunoproteomics and metagenomics. Secondly, systems biomedicine analyses are essential to unravel the complex interactions between these cellular networks, pathways, and the multifactorial trigger factors and to delineate new drug targets in the cellular networks or pathways. Drug discovery processes should delineate new drugs targeting the intracellular networks and immune-related pathways.]]>
Sat, 02 May 2015 00:00:00 PDT
First trimester vitamin D status and placental epigenomics in preeclampsia among Northern Plains primiparas. Anderson CM, Ralph JL, Johnson L, Scheett A, Wright ML, Taylor JY, Ohm JE, Uthus E
Life Sci (May 2015)

As maternal vitamin D status has been associated with preeclampsia, the purpose of this study was to determine variations in DNA methylation patterns and associated protein expression in placental genes regulating vitamin D metabolism.]]>
Wed, 29 Apr 2015 00:00:00 PDT
Epigenetics and cardiovascular disease. Delbridge LM, Mellor KM, Wold LE
Life Sci (May 2015)

Wed, 29 Apr 2015 00:00:00 PDT
Molecular mechanisms of ethanol-associated oro-esophageal squamous cell carcinoma. Liu Y, Chen H, Sun Z, Chen X
Cancer Lett (Jun 2015)

Alcohol drinking is a major etiological factor of oro-esophageal squamous cell carcinoma (OESCC). Both local and systemic effects of ethanol may promote carcinogenesis, especially among chronic alcoholics. However, molecular mechanisms of ethanol-associated OESCC are still not well understood. In this review, we summarize current understandings and propose three mechanisms of ethanol-associated OESCC: (1) Disturbance of systemic metabolism of nutrients: during ethanol metabolism in the liver, systemic metabolism of retinoids, zinc, iron and methyl groups is altered. These nutrients are known to be associated with the development of OESCC. (2) Disturbance of redox metabolism in squamous epithelial cells: when ethanol is metabolized in oro-esophageal squamous epithelial cells, reactive oxygen species are generated and produce oxidative damage. Meanwhile, ethanol may also disturb fatty-acid metabolism in these cells. (3) Disturbance of signaling pathways in squamous epithelial cells: due to its physico-chemical properties, ethanol changes cell membrane fluidity and shape, and may thus impact multiple signaling pathways. Advanced molecular techniques in genomics, epigenomics, metabolomics and microbiomics will help us elucidate how ethanol promotes OESCC.]]>
Sat, 04 Apr 2015 00:00:00 PDT
The role dietary of bioactive compounds on the regulation of histone acetylases and deacetylases: a review. Vahid F, Zand H, Nosrat-Mirshekarlou E, Najafi R, Hekmatdoost A
Gene (May 2015)

Nutrigenomics is an area of epigenomics that explores and defines the rapidly evolving field of diet-genome interactions. Lifestyle and diet can significantly influence epigenetic mechanisms, which cause heritable changes in gene expression without changes in DNA sequence. Nutrient-dependent epigenetic variations can significantly affect genome stability, mRNA and protein expression, and metabolic changes, which in turn influence food absorption and the activity of its constituents. Dietary bioactive compounds can affect epigenetic alterations, which are accumulated over time and are shown to be involved in the pathogenesis of age-related diseases such as diabetes, cancer, and cardiovascular disease. Histone acetylation is an epigenetic modification mediated by histone acetyl transferases (HATs) and histone deacetylases (HDACs) critically involved in regulating affinity binding between the histones and DNA backbone. The HDAC-mediated increase in histone affinity to DNA causes DNA condensation, preventing transcription, whereas HAT-acetylated chromatin is transcriptionally active. HDAC and HAT activities are reported to be associated with signal transduction, cell growth and death, as well as with the pathogenesis of various diseases. The aim of this review was to evaluate the role of diet and dietary bioactive compounds on the regulation of HATs and HDACs in epigenetic diseases. Dietary bioactive compounds such as genistein, phenylisothiocyanate, curcumin, resveratrol, indole-3-carbinol, and epigallocatechin-3-gallate can regulate HDAC and HAT activities and acetylation of histones and non-histone chromatin proteins, and their health benefits are thought to be attributed to these epigenetic mechanisms. The intake of dietary compounds that regulate epigenetic modifications can provide significant health effects and may prevent various pathological processes involved in the development of cancer and other life-threatening diseases.]]>
Fri, 20 Mar 2015 00:00:00 PDT
Epigenetic modifications as regulatory elements of autophagy in cancer. Sui X, Zhu J, Zhou J, Wang X, Li D, Han W, Fang Y, Pan H
Cancer Lett (May 2015)

Epigenetic modifications have been considered as hallmarks of cancer and play an important role in tumor initiation and development. Epigenetic mechanisms, including DNA methylation, histone modifications, and microRNAs, may regulate cell cycle and apoptosis, as well as macroautophagy (hereafter referred to as autophagy). Autophagy, as a crucial cellular homeostatic mechanism, performs a dual role, having pro-survival or pro-death properties. A variety of signaling pathways including epigenetic control have been implicated in the upregulation or downregulation of autophagy. However, the role of epigenetic regulation in autophagy is still less well acknowledged. Recent studies have linked epigenetic control to the autophagic process. Some epigenetic modifiers are also involved in the regulation of autophagy and potentiate the efficacy of traditional therapeutics. Thus, understanding the novel functions of epigenetic control in autophagy may allow us to develop potential therapeutic approaches for cancer treatment.]]>
Mon, 16 Mar 2015 00:00:00 PDT