'; ?> 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 Sat, 25 Apr 2015 02:15:28 PDT Sat, 25 Apr 2015 02:15:28 PDT jirtle@radonc.duke.edu james001@jirtle.com Chromatin mechanisms in the developmental control of imprinted gene expression. Sanli I, Feil R
Int J Biochem Cell Biol (Apr 2015)

Hundreds of protein-coding genes and regulatory non-coding RNAs (ncRNAs) are subject to genomic imprinting. The mono-allelic DNA methylation marks that control imprinted gene expression are somatically maintained throughout development, and this process is linked to specific chromatin features. Yet, at many imprinted genes, the mono-allelic expression is lineage or tissue-specific. Recent studies provide mechanistic insights into the developmentally-restricted action of the 'imprinting control regions' (ICRs). At several imprinted domains, the ICR expresses a long ncRNA that mediates chromatin repression in cis (and probably in trans as well). ICRs at other imprinted domains mediate higher-order chromatin structuration that enhances, or prevents, transcription of close-by genes. Here, we present how chromatin and ncRNAs contribute to developmental control of imprinted gene expression and discuss implications for disease. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease.]]>
Fri, 24 Apr 2015 00:00:00 PDT
A DNA ligase required for active DNA demethylation and genomic imprinting in Arabidopsis. Li Y, Duan CG, Zhu X, Qian W, Zhu JK
Cell Res (Apr 2015)

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Fri, 24 Apr 2015 00:00:00 PDT
The genetic basis of peripheral arterial disease: current knowledge, challenges, and future directions. Kullo IJ, Leeper NJ
Circ Res (Apr 2015)

Several risk factors for atherosclerotic peripheral arterial disease (PAD), such as dyslipidemia, diabetes mellitus, and hypertension, are heritable. However, predisposition to PAD may be influenced by genetic variants acting independently of these risk factors. Identification of such genetic variants will provide insights into underlying pathophysiologic mechanisms and facilitate the development of novel diagnostic and therapeutic approaches. In contrast to coronary heart disease, relatively few genetic variants that influence susceptibility to PAD have been discovered. This may be, in part, because of greater clinical and genetic heterogeneity in PAD. In this review, we (1) provide an update on the current state of knowledge about the genetic basis of PAD, including results of family studies and candidate gene, linkage as well as genome-wide association studies; (2) highlight the challenges in investigating the genetic basis of PAD and possible strategies to overcome these challenges; and (3) discuss the potential of genome sequencing, RNA sequencing, differential gene expression, epigenetic profiling, and systems biology in increasing our understanding of the molecular genetics of PAD.]]>
Fri, 24 Apr 2015 00:00:00 PDT
How did viviparity originate and evolve? Of conflict, co-option, and cryptic choice. Kalinka AT
Bioessays (Apr 2015)

I propose that the underlying adaptation enabling the reproductive strategy of birthing live young (viviparity) is retraction of the site of fertilization within the female reproductive tract, and that this evolved as a means of postcopulatory sexual selection. There are three conspicuous aspects associated with viviparity: (i) internal development is a complex trait often accompanied by a suite of secondary adaptations, yet it is unclear how the intermediate state of this trait - egg retention - could have evolved; (ii) viviparity often results in a reduction in fecundity; (iii) viviparity has evolved independently many times across a diverse array of animal groups. Focusing on the Diptera (true flies), I provide explanations for these observations. I further propose that fecundity is not traded-off to enable potential benefits of viviparity, but rather that loss of fecundity is directly selected and egg retention is an indirect consequence - a model that provides a unifying common basis for the ubiquity of viviparity.]]>
Thu, 23 Apr 2015 00:00:00 PDT
Maternal and zygotic Zfp57 modulate NOTCH signaling in cardiac development. Shamis Y, Cullen DE, Liu L, Yang G, Ng SF, Xiao L, Bell FT, Ray C, Takikawa S, Moskowitz IP, Cai CL, Yang X, Li X
Proc Natl Acad Sci U S A (Apr 2015)

Zfp57 is a maternal-zygotic effect gene that maintains genomic imprinting. Here we report that Zfp57 mutants exhibited a variety of cardiac defects including atrial septal defect (ASD), ventricular septal defect (VSD), thin myocardium, and reduced trabeculation. Zfp57 maternal-zygotic mutant embryos displayed more severe phenotypes with higher penetrance than the zygotic ones. Cardiac progenitor cells exhibited proliferation and differentiation defects in Zfp57 mutants. ZFP57 is a master regulator of genomic imprinting, so the DNA methylation imprint was lost in embryonic heart without ZFP57. Interestingly, the presence of imprinted DLK1, a target of ZFP57, correlated with NOTCH1 activation in cardiac cells. These results suggest that ZFP57 may modulate NOTCH signaling during cardiac development. Indeed, loss of ZFP57 caused loss of NOTCH1 activation in embryonic heart with more severe loss observed in the maternal-zygotic mutant. Maternal and zygotic functions of Zfp57 appear to play redundant roles in NOTCH1 activation and cardiomyocyte differentiation. This serves as an example of a maternal effect that can influence mammalian organ development. It also links genomic imprinting to NOTCH signaling and particular developmental functions.]]>
Wed, 22 Apr 2015 00:00:00 PDT
Non-germline Restoration of Genomic Imprinting for a Small Subset of Imprinted Genes in Ubiquitin-like PHD and RING Finger Domain-Containing 1 (Uhrf1) Null Mouse Embryonic Stem Cells. Qi S, Wang Z, Li P, Wu Q, Shi T, Li J, Wong J
J Biol Chem (Apr 2015)

The underlying mechanism for the establishment and maintenance of differential DNA methylation in imprinted genes is largely unknown. Previous studies using Dnmt1 knockout ES cells demonstrated that, while re-expression of DNMT1 restored DNA methylation in the non-imprinted regions, the methylation patterns of imprinted genes could only be restored through germ-line passage. Knockout of Uhrf1, an accessory factor essential for DNMT1-mediated DNA methylation, in mouse ES cells also led to impaired global DNA methylation and loss of genomic imprinting. Here we demonstrated that, although re-expression of UHRF1 in Uhrf1-/- ES cells restored DNA methylation for the bulk genome but not for most of the imprinted genes, it did rescue DNA methylation for imprinted H19, Nnat and Dlk1 genes. Analysis of histone modifications at the differential methylated regions (DMRs) of the imprinting genes by chromatin immunoprecipitation (ChIP) assays revealed that for the imprinted genes whose DNA methylation could be restored upon re-expression of UHRF1, the active histone marks especially H3K4me3 were maintained at considerably low and maintained the low levels even in the Uhrf1-/- ES cells. In contrast, for the imprinted genes whose DNA methylation could not be restored upon UHRF1 re-expression, the active histone marks especially H3K4me3 were relatively high and became even higher in the Uhrf1-/- ES cells. Our study thus supports a role for histone modifications in determining the establishment of imprinting-related DNA methylation and demonstrates that mouse ES cells can be a valuable model for mechanistic study of establishment and maintenance of differential DNA methylation in imprinted genes.]]>
Wed, 22 Apr 2015 00:00:00 PDT
Emerging technologies for studying DNA methylation for the molecular diagnosis of cancer. Marzese DM, Hoon DS
Expert Rev Mol Diagn (May 2015)

DNA methylation is an epigenetic mechanism that plays a key role in regulating gene expression and other functions. Although this modification is seen in different sequence contexts, the most frequently detected DNA methylation in mammals involves cytosine-guanine dinucleotides. Pathological alterations in DNA methylation patterns are described in a variety of human diseases, including cancer. Unlike genetic changes, DNA methylation is heavily influenced by subtle modifications in the cellular microenvironment. In all cancers, aberrant DNA methylation is involved in the alteration of a large number of oncological pathways with relevant theranostic utility. Several technologies for DNA methylation mapping have been developed recently and successfully applied in cancer studies. The scope of these technologies varies from assessing a single cytosine-guanine locus to genome-wide distribution of DNA methylation. Here, we review the strengths and weaknesses of these approaches in the context of clinical utility for the molecular diagnosis of human cancers.]]>
Tue, 21 Apr 2015 00:00:00 PDT
Genetic conflict reflected in tissue-specific maps of genomic imprinting in human and mouse. Babak T, DeVeale B, Tsang EK, Zhou Y, Li X, Smith KS, Kukurba KR, Zhang R, Li JB, van der Kooy D, Montgomery SB, Fraser HB
Nat Genet (Apr 2015)

Genomic imprinting is an epigenetic process that restricts gene expression to either the maternally or paternally inherited allele. Many theories have been proposed to explain its evolutionary origin, but understanding has been limited by a paucity of data mapping the breadth and dynamics of imprinting within any organism. We generated an atlas of imprinting spanning 33 mouse and 45 human developmental stages and tissues. Nearly all imprinted genes were imprinted in early development and either retained their parent-of-origin expression in adults or lost it completely. Consistent with an evolutionary signature of parental conflict, imprinted genes were enriched for coexpressed pairs of maternally and paternally expressed genes, showed accelerated expression divergence between human and mouse, and were more highly expressed than their non-imprinted orthologs in other species. Our approach demonstrates a general framework for the discovery of imprinting in any species and sheds light on the causes and consequences of genomic imprinting in mammals.]]>
Mon, 20 Apr 2015 00:00:00 PDT
The childhood solid tumor network: A new resource for the developmental biology and oncology research communities. Stewart E, Federico S, Karlstrom A, Shelat A, Sablauer A, Pappo A, Dyer MA
Dev Biol (Apr 2015)

Significant advances have been made over the past 25 years in our understanding of the most common adult solid tumors such as breast, colon, lung and prostate cancer. Much less is known about childhood solid tumors because they are rare and because they originate in developing organs during fetal development, childhood and adolescence. It can be very difficult to study the cellular origins of pediatric solid tumors in developing organs characterized by rapid proliferative expansion, growth factor signaling, developmental angiogenesis, programmed cell death, tissue reorganization and cell migration. Not only has the etiology of pediatric cancer remained elusive because of their developmental origins, but it also makes it more difficult to treat. Molecular targeted therapeutics that alter developmental pathway signaling may have devastating effects on normal organ development. Therefore, basic research focused on the mechanisms of development provides an essential foundation for pediatric solid tumor translational research. In this article, we describe new resources available for the developmental biology and oncology research communities. In a companion paper, we present the detailed characterization of an orthotopic xenograft of a pediatric solid tumor derived from sympathoadrenal lineage during development.]]>
Sun, 19 Apr 2015 00:00:00 PDT
Polycomb Repressive Complex 2 epigenomic signature defines age-associated hypermethylation and gene expression changes. Dozmorov MG
Epigenetics (Apr 2015)

Although age-associated gene expression and methylation changes have been reported throughout the literature, the unifying epigenomic principles of aging remain poorly understood. Recent explosion in availability and resolution of functional/regulatory genome annotation data (epigenomic data), such as that provided by the ENCODE and Roadmap Epigenomics projects, provides an opportunity for the identification of epigenomic mechanisms potentially altered by age-associated differentially methylated regions (aDMRs) and to find regulatory signatures in the promoters of age-associated genes (aGENs). In this study we found that aDMRs and aGENs identified in multiple independent studies share a common Polycomb Repressive Complex 2 signature marked by EZH2, SUZ12, CTCF binding sites, repressive H3K27me3, and activating H3K4me1 histone modification marks, and a "poised promoter" chromatin state. This signature is depleted in RNAP II-associated transcription factor binding sites, activating H3K79me2, H3K36me3, H3K27ac marks, and an "active promoter" chromatin state. The PRC2 signature was shown to be generally stable across cell types. When considering the directionality of methylation changes, we found the PRC2 signature to be associated with aDMRs hypermethylated with age, while hypomethylated aDMRs were associated with enhancers. In contrast, aGENs were associated with the PRC2 signature independently of the directionality of gene expression changes. In this study we demonstrate that the PRC2 signature is the common epigenomic context of genomic regions associated with hypermethylation and gene expression changes in aging.]]>
Thu, 16 Apr 2015 00:00:00 PDT
Characterization of global loss of imprinting in fetal overgrowth syndrome induced by assisted reproduction. Chen Z, Hagen DE, Elsik CG, Ji T, Morris CJ, Moon LE, Rivera RM
Proc Natl Acad Sci U S A (Apr 2015)

Embryos generated with the use of assisted reproductive technologies (ART) can develop overgrowth syndromes. In ruminants, the condition is referred to as large offspring syndrome (LOS) and exhibits variable phenotypic abnormalities including overgrowth, enlarged tongue, and abdominal wall defects. These characteristics recapitulate those observed in the human loss-of-imprinting (LOI) overgrowth syndrome Beckwith-Wiedemann (BWS). We have recently shown LOI at the KCNQ1 locus in LOS, the most common epimutation in BWS. Although the first case of ART-induced LOS was reported in 1995, studies have not yet determined the extent of LOI in this condition. Here, we determined allele-specific expression of imprinted genes previously identified in human and/or mouse in day ∼105 Bos taurus indicus × Bos taurus taurus F1 hybrid control and LOS fetuses using RNAseq. Our analysis allowed us to determine the monoallelic expression of 20 genes in tissues of control fetuses. LOS fetuses displayed variable LOI compared with controls. Biallelic expression of imprinted genes in LOS was associated with tissue-specific hypomethylation of the normally methylated parental allele. In addition, a positive correlation was observed between body weight and the number of biallelically expressed imprinted genes in LOS fetuses. Furthermore, not only was there loss of allele-specific expression of imprinted genes in LOS, but also differential transcript amounts of these genes between control and overgrown fetuses. In summary, we characterized previously unidentified imprinted genes in bovines and identified misregulation of imprinting at multiple loci in LOS. We concluded that LOS is a multilocus LOI syndrome, as is BWS.]]>
Wed, 15 Apr 2015 00:00:00 PDT
Formalin-fixed, paraffin-embedded (FFPE) tissue epigenomics using Infinium HumanMethylation450 BeadChip assays. de Ruijter TC, de Hoon JP, Slaats J, de Vries B, Janssen MJ, van Wezel T, Aarts MJ, van Engeland M, Tjan-Heijnen VC, Van Neste L, Veeck J
Lab Invest (Apr 2015)

Current genome-wide methods to detect DNA-methylation in healthy and diseased tissue require high-quality DNA from fresh-frozen (FF) samples. However, well-annotated clinical samples are mostly available as formalin-fixed, paraffin-embedded (FFPE) tissues containing poor-quality DNA. To overcome this limitation, we here aimed to evaluate a DNA restoration protocol for usage with the genome-wide Infinium HumanMethylation450 BeadChip assay (HM-450K). Sixty-six DNA samples from normal colon (n=9) and breast cancer (n=11) were interrogated separately using HM-450K. Analyses included matched FF/FFPE samples and technical duplicates. FFPE DNA was processed with (FFPEr) or without a DNA restoration protocol (Illumina). Differentially methylated genes were finally validated in 24 additional FFPE tissues using nested methylation-specific PCR (MSP). In summary, β-values correlation between FFPEr duplicates was high (ρ=0.9927 (s.d. ±0.0015)). Matched FF/FFPEr correlation was also high (ρ=0.9590 (s.d. ±0.0184)) compared with matched FF/FFPE (ρ=0.8051 (s.d. ±0.1028). Probe detection rate in FFPEr samples (98.37%, s.d. ±0.66) was comparable to FF samples (99.98%, s.d. ±0.019) and substantially lower in FFPE samples (82.31%, s.d. ±18.65). Assay robustness was not decreased by sample archival age up to 10 years. We could also demonstrate no decrease in assay robustness when using 100 ng of DNA input only. Four out of the five selected differentially methylated genes could be validated by MSP. The gene failing validation by PCR showed high variation of CpG β-values in primer-binding sites. In conclusion, by using the FFPE DNA restoration protocol, HM-450K assays provide robust, accurate and reproducible results with FFPE tissue-derived DNA, which are comparable to those obtained with FF tissue. Most importantly, differentially methylated genes can be validated using more sensitive techniques, such as nested MSP, altogether providing an epigenomics platform for molecular pathological epidemiology research on archived samples with limited tissue amount.Laboratory Investigation advance online publication, 13 April 2015; doi:10.1038/labinvest.2015.53.]]>
Mon, 13 Apr 2015 00:00:00 PDT
Germline and somatic imprinting in the nonhuman primate highlights species differences in oocyte methylation. Cheong CY, Chng K, Ng S, Chew SB, Chan L, Ferguson-Smith AC
Genome Res (Apr 2015)

Genomic imprinting is an epigenetic mechanism resulting in parental allele-specific gene expression. Defects in normal imprinting are found in cancer, assisted reproductive technologies, and several human syndromes. In mouse models, germline-derived DNA methylation is shown to regulate imprinting. Though imprinting is largely conserved between mammals, species- and tissue-specific domains of imprinted expression exist. Using the cynomolgus macaque (Macaca fascicularis) to assess primate-specific imprinting, we present a comprehensive view of tissue-specific imprinted expression and DNA methylation at established imprinted gene clusters. For example, like mouse and unlike human, macaque IGF2R is consistently imprinted, and the PLAGL1, INPP5F transcript variant 2, and PEG3 imprinting control regions are not methylated in the macaque germline but acquire this post-fertilization. Methylome data from human early embryos appear to support this finding. These suggest fundamental differences in imprinting control mechanisms between primate species and rodents at some imprinted domains, with implications for our understanding of the epigenetic programming process in humans and its influence on disease.]]>
Sat, 11 Apr 2015 00:00:00 PDT
Allelic Imbalance Is a Prevalent and Tissue-Specific Feature of the Mouse Transcriptome. Pinter SF, Colognori D, Beliveau BJ, Sadreyev RI, Payer B, Yildirim E, Wu CT, Lee JT
Genetics (Apr 2015)

In mammals, several classes of monoallelic genes have been identified, including those subject to X-chromosome inactivation (XCI), genomic imprinting, and random monoallelic expression (RMAE). However, the extent to which these epigenetic phenomena are influenced by underlying genetic variation is unknown. Here we perform a systematic classification of allelic imbalance in mouse hybrids derived from reciprocal crosses of divergent strains. We observe that deviation from balanced biallelic expression is common, occurring in ~20% of the mouse transcriptome in a given tissue. Allelic imbalance attributed to genotypic variation is by far the most prevalent class and typically is tissue-specific. However, some genotype-based imbalance is maintained across tissues and is associated with greater genetic variation, especially in 5' and 3' termini of transcripts. We further identify novel random monoallelic and imprinted genes, and find that genotype can modify penetrance of parental origin even in the setting of large imprinted regions. Examination of nascent transcripts in single cells from inbred parental strains reveals that genes showing genotype-based imbalance in hybrids can also exhibit monoallelic expression in isogenic backgrounds. This surprising observation may suggest a competition between alleles and/or reflect the combined impact of cis- and trans-acting variation on expression of a given gene. Our findings provide novel insights into gene regulation and may be relevant to human genetic variation and disease.]]>
Sat, 11 Apr 2015 00:00:00 PDT
Epigenomics, gestational programming and risk of metabolic syndrome. Desai M, Jellyman JK, Ross MG
Int J Obes (Lond) (Apr 2015)

Epigenetic mechanisms are emerging as mediators linking early environmental exposures during pregnancy with programmed changes in gene expression that alter offspring growth and development. There is irrefutable evidence from human and animal studies that nutrient and environmental agent exposures (for example, endocrine disruptors) during pregnancy may affect fetal/newborn development resulting in offspring obesity and obesity-associated metabolic abnormalities (metabolic syndrome). This concept of 'gestational programming' is associated with alterations to the epigenome (nongenomic) rather than changes in the DNA sequence (genomic). Epigenetic alterations induced by suboptimal maternal nutrition/endocrine factors include DNA methylation, histone modifications, chromatin remodeling and/or regulatory feedback by microRNAs, all of which have the ability to modulate gene expression and promote the metabolic syndrome phenotype. Recent studies have shown tissue-specific transcriptome patterns and phenotypes not only in the exposed individual, but also in subsequent progeny. Notably, the transmission of gestational programming effects to subsequent generations occurs in the absence of continued adverse environmental exposures, thus propagating the cycle of obesity and metabolic syndrome. This phenomenon may be attributed to an extrinsic process resulting from the maternal phenotype and the associated nutrient alterations occurring within each pregnancy. In addition, epigenetic inheritance may occur through somatic cells or through the germ line involving both maternal and paternal lineages. Since epigenetic gene modifications may be reversible, understanding how epigenetic mechanisms contribute to transgenerational transmission of obesity and metabolic dysfunction is crucial for the development of novel early detection and prevention strategies for programmed metabolic syndrome. In this review we discuss the evidence in human and animal studies for the role of epigenomic mechanisms in the transgenerational transmission of programmed obesity and metabolic syndrome.]]>
Tue, 07 Apr 2015 00:00:00 PDT
Nucleotide substitutions revealing specific functions of Polycomb group genes. Bajusz I, Sipos L, Pirity MK
Mol Genet Metab (Apr 2015)

POLYCOMB group (PCG) proteins belong to the family of epigenetic regulators of genes playing important roles in differentiation and development. Mutants of PcG genes were isolated first in the fruit fly, Drosophila melanogaster, resulting in spectacular segmental transformations due to the ectopic expression of homeotic genes. Homologs of Drosophila PcG genes were also identified in plants and in vertebrates and subsequent experiments revealed the general role of PCG proteins in the maintenance of the repressed state of chromatin through cell divisions. The past decades of gene targeting experiments have allowed us to make significant strides towards understanding how the network of PCG proteins influences multiple aspects of cellular fate determination during development. Being involved in the transmission of specific expression profiles of different cell lineages, PCG proteins were found to control wide spectra of unrelated epigenetic processes in vertebrates, such as stem cell plasticity and renewal, genomic imprinting and inactivation of X-chromosome. PCG proteins also affect regulation of metabolic genes being important for switching programs between pluripotency and differentiation. Insight into the precise roles of PCG proteins in normal physiological processes has emerged from studies employing cell culture-based systems and genetically modified animals. Here we summarize the findings obtained from PcG mutant fruit flies and mice generated to date with a focus on PRC1 and PRC2 members altered by nucleotide substitutions resulting in specific alleles. We also include a compilation of lessons learned from these models about the in vivo functions of this complex protein family. With multiple knockout lines, sophisticated approaches to study the consequences of peculiar missense point mutations, and insights from complementary gain-of-function systems in hand, we are now in a unique position to significantly advance our understanding of the molecular basis of in vivo functions of PcG proteins.]]>
Tue, 07 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
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 (Apr 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.]]>
Fri, 03 Apr 2015 00:00:00 PDT
Epigenetics and Its Role in Periodontal Diseases: A State-of-the-Art Review. Larsson L, Castilho RM, Giannobile WV
J Periodontol (Apr 2015)

The immune response to oral bacteria and the subsequent activation of inflammatory signaling is not only dependent on genetic factors. The importance of so-called epigenetic mechanisms presents additional regulatory pathways of genes involved in maintaining chronic inflammation, including gingivitis and periodontitis. The term epigenetics relates to changes in gene expression that are not encoded in the DNA sequence itself and include chemical alterations of DNA and its associated proteins. These changes lead to remodeling of the chromatin and subsequent activation or inactivation of a gene. Epigenetic mechanisms have been found to contribute to disease, including cancer and autoimmune or inflammatory diseases. In this state-of-the art review, the authors provide the latest findings on the involvement of epigenetic modifications in the development of periodontal disease and present emerging therapeutic strategies aimed at epigenetic targets (epidrugs) associated with the disruption of tissue homeostasis and the development of periodontitis.]]>
Wed, 01 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