'; ?> 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, 20 Nov 2018 15:46:54 EST Tue, 20 Nov 2018 15:46:54 EST jirtle@radonc.duke.edu james001@jirtle.com Early Life Stress and Epigenetics in Late-onset Alzheimer's Dementia: A Systematic Review. Lemche E
Curr Genomics (Nov 2018)

Involvement of life stress in Late-Onset Alzheimer's Disease (LOAD) has been evinced in longitudinal cohort epidemiological studies, and endocrinologic evidence suggests involvements of catecholamine and corticosteroid systems in LOAD. Early Life Stress (ELS) rodent models have successfully demonstrated sequelae of maternal separation resulting in LOAD-analogous pathology, thereby supporting a role of insulin receptor signalling pertaining to GSK-3beta facilitated tau hyper-phosphorylation and amyloidogenic processing. Discussed are relevant ELS studies, and findings from three mitogen-activated protein kinase pathways (JNK/SAPK pathway, ERK pathway, p38/MAPK pathway) relevant for mediating environmental stresses. Further considered were the roles of autophagy impairment, neuroinflammation, and brain insulin resistance. For the meta-analytic evaluation, 224 candidate gene loci were extracted from reviews of animal studies of LOAD pathophysiological mechanisms, of which 60 had no positive results in human LOAD association studies. These loci were combined with 89 gene loci confirmed as LOAD risk genes in previous GWAS and WES. Of the 313 risk gene loci evaluated, there were 35 human reports on epigenomic modifications in terms of methylation or histone acetylation. 64 microRNA gene regulation mechanisms were published for the compiled loci. Genomic association studies support close relations of both noradrenergic and glucocorticoid systems with LOAD. For HPA involvement, a CRHR1 haplotype with MAPT was described, but further association of only HSD11B1 with LOAD found; however, association of FKBP1 and NC3R1 polymorphisms was documented in support of stress influence to LOAD. In the brain insulin system, IGF2R, INSR, INSRR, and plasticity regulator ARC, were associated with LOAD. Pertaining to compromised myelin stability in LOAD, relevant associations were found for BIN1, RELN, SORL1, SORCS1, CNP, MAG, and MOG. Regarding epigenetic modifications, both methylation variability and de-acetylation were reported for LOAD. The majority of up-to-date epigenomic findings include reported modifications in the well-known LOAD core pathology loci MAPT, BACE1, APP (with FOS, EGR1), PSEN1, PSEN2, and highlight a central role of BDNF. Pertaining to ELS, relevant loci are FKBP5, EGR1, GSK3B; critical roles of inflammation are indicated by CRP, TNFA, NFKB1 modifications; for cholesterol biosynthesis, DHCR24; for myelin stability BIN1, SORL1, CNP; pertaining to (epi)genetic mechanisms, hTERT, MBD2, DNMT1, MTHFR2. Findings on gene regulation were accumulated for BACE1, MAPK signalling, TLR4, BDNF, insulin signalling, with most reports for miR-132 and miR-27. Unclear in epigenomic studies remains the role of noradrenergic signalling, previously demonstrated by neuropathological findings of childhood nucleus caeruleus degeneration for LOAD tauopathy.]]>
Wed, 31 Dec 1969 19:00:00 EST
Evolutionary Quantitative Genetics of Genomic Imprinting. O'Brien EK, Wolf JB
Genetics (Nov 2018)

Genomic imprinting shapes the genotype-phenotype relationship by creating an asymmetry between the influences of paternally and maternally inherited gene copies. Consequently, imprinting can impact heritable and nonheritable variation, resemblance of relatives, and evolutionary dynamics. Although previous analyses have identified some of the quantitative genetic consequences of imprinting, we lack a framework that cleanly separates the influence of imprinting from other components of variation, particularly dominance. Here we apply a simple orthogonal genetic model to evaluate the roles of genetic (additive and dominance) and epigenetic (imprinting) effects. Imprinting increases the resemblance of relatives who share the expressed allele, and therefore increases variance among families of full or half-siblings. However, only part of this increased variance is heritable and contributes to selection responses. When selection is within or among families sharing only a single parent (half-siblings), which is common in selective breeding programs, imprinting can alter overall responses. Selection is more efficient when it acts among families sharing the expressed parent, or within families sharing the parent with lower expression. Imprinting also affects responses to sex-specific selection. When selection is on the sex whose gene copy has lower expression, the response is diminished or delayed the next generation, although the long-term response is unaffected. Our findings have significant implications for understanding patterns of variation, interpretation of short-term selection responses, and the efficacy of selective breeding programs, demonstrating the importance of considering the independent influence of genomic imprinting in quantitative genetics.]]>
Wed, 31 Dec 1969 19:00:00 EST
Eating According to One's Genes? Exploring the French Public's Understanding of and Reactions to Personalized Nutrition. Fournier T, Poulain JP
Qual Health Res (Dec 2018)

In this article, we analyze qualitatively the understanding of and reactions to personalized nutrition (PN) among the French public. Focus groups were conducted to identify the opinions and discourses about two applications of knowledge from nutritional (epi)genomics: a biotechnology (nutrigenetic testing) and a public awareness campaign (the "first thousand days of life" initiative). Our objective was to understand to what extent PN could lead to changes in eating practices as well as in the representations of food-health relationships within France, a country characterized by a strong commitment to commensality and a certain "nutritional relativism." Although discourses on nutritional genomics testify to a resistance to food medicalization, nutritional epigenomics appears as more performative because it introduces the question of transgenerational transmission, thus parental responsibility.]]>
Wed, 31 Dec 1969 19:00:00 EST
Recent progress, methods and perspectives in forensic epigenetics. Vidaki A, Kayser M
Forensic Sci Int Genet (Nov 2018)

Forensic epigenetics, i.e., investigating epigenetics variation to resolve forensically relevant questions unanswerable with standard forensic DNA profiling has been gaining substantial ground over the last few years. Differential DNA methylation among tissues and individuals has been proposed as useful resource for three forensic applications i) determining the tissue type of a human biological trace, ii) estimating the age of an unknown trace donor, and iii) differentiating between monozygotic twins. Thus far, forensic epigenetic investigations have used a wide range of methods for CpG marker discovery, prediction modelling and targeted DNA methylation analysis, all coming with advantages and disadvantages when it comes to forensic trace analysis. In this review, we summarize the most recent literature on these three main topics of current forensic epigenetic investigations and discuss limitations and practical considerations in experimental design and data interpretation, such as technical and biological biases. Moreover, we provide future perspectives with regard to new research questions, new epigenetic markers and recent technological advances that - as we envision - will move the field towards forensic epigenomics in the near future.]]>
Wed, 31 Dec 1969 19:00:00 EST
Analysis of the Paternally-Imprinted DLK1-MEG3 and IGF2-H19 Tandem Gene Loci in NT2 Embryonal Carcinoma Cells Identifies DLK1 as a Potential Therapeutic Target. Sellers ZP, Schneider G, Maj M, Ratajczak MZ
Stem Cell Rev (Dec 2018)

The paternally-imprinted genes insulin-like growth factor 2 (IGF2), H19, delta-like homologue 1 (DLK1), and maternally-expressed gene 3 (MEG3) are expressed from the tandem gene loci IGF2-H19 and DLK1-MEG3, which play crucial roles in initiating embryogenesis and development. The erasure of imprinting (EOI) at differentially methylated regions (DMRs) which regulate the expression of these genes maintains the developmental quiescence of primordial germ cells (PGCs) migrating through the embryo proper during embryogenesis and prevents them from forming teratomas. To address the potential involvement of the IGF2-H19 and DLK1-MEG3 loci in the pathogenesis of embryonal carcinoma (EC), we investigated their genomic imprinting at DMRs in the human PGC-derived EC cell line NTera-2 (NT2). We observed EOI at the IGF2-H19 locus and, somewhat to our surprise, a loss of imprinting (LOI) at the DLK1-MEG3 locus. As a result, NT2 cells express imprinted gene ratios from these loci such that there are i) low levels of the proliferation-promoting IGF2 relative to ii) high levels of the proliferation-inhibiting long noncoding RNA (lncRNA) H19 and iii) high levels of proliferation-promoting DLK1 relative to iv) low levels of the proliferation-inhibiting lncRNA MEG3. Consistent with this pattern of expression, the knockdown of DLK1 mRNA by shRNA resulted in decreased in vitro cell proliferation and in vivo tumor growth as well as decreased in vivo organ seeding by NT2 cells. Furthermore, treatment of NT2 cells with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-azaD) inhibited their proliferation. This inhibition was accompanied by changes in expression of both tandem gene sets: a decrease in the expression of DLK1 and upregulation of the proliferation-inhibiting lncRNA MEG3, and at the same time upregulation of IGF2 and downregulation of the lncRNA H19. These results suggest that the DLK1-MEG3 locus, and not the IGF2-H19 locus, drives the tumorigenicity of NT2 cells. Based on these results, we identified DLK1 as a novel treatment target for EC that could be downregulated by 5-azaD.]]>
Wed, 31 Dec 1969 19:00:00 EST
Generation of Bimaternal and Bipaternal Mice from Hypomethylated Haploid ESCs with Imprinting Region Deletions. Li ZK, Wang LY, Wang LB, Feng GH, Yuan XW, Liu C, Xu K, Li YH, Wan HF, Zhang Y, Li YF, Li X, Li W, Zhou Q, Hu BY
Cell Stem Cell (Nov 2018)

Unisexual reproduction is widespread among lower vertebrates, but not in mammals. Deletion of the H19 imprinted region in immature oocytes produced bimaternal mice with defective growth; however, bipaternal reproduction has not been previously achieved in mammals. We found that cultured parthenogenetic and androgenetic haploid embryonic stem cells (haESCs) display DNA hypomethylation resembling that of primordial germ cells. Through MII oocyte injection or sperm coinjection with hypomethylated haploid ESCs carrying specific imprinted region deletions, we obtained live bimaternal and bipaternal mice. Deletion of 3 imprinted regions in parthenogenetic haploid ESCs restored normal growth of fertile bimaternal mice, whereas deletion of 7 imprinted regions in androgenetic haploid ESCs enabled production of live bipaternal mice that died shortly after birth. Phenotypic analyses of organ and body size of these mice support the genetic conflict theory of genomic imprinting. Taken together, our results highlight the factors necessary for crossing same-sex reproduction barriers in mammals.]]>
Wed, 31 Dec 1969 19:00:00 EST
TBX2 is a neuroblastoma core regulatory circuitry component enhancing MYCN/FOXM1 reactivation of DREAM targets. Decaesteker B, Denecker G, Van Neste C, Dolman EM, Van Loocke W, Gartlgruber M, Nunes C, De Vloed F, Depuydt P, Verboom K, Rombaut D, Loontiens S, De Wyn J, Kholosy WM, Koopmans B, Essing AHW, Herrmann C, Dreidax D, Durinck K, Deforce D, van Nieuwerburgh F, Henssen A, Versteeg R, Boeva V, Schleiermacher G, van Nes J, Mestdagh P, Vanhauwaert S, Schulte JH, Westermann F, Molenaar JJ, De Preter K, Speleman F
Nat Commun (Nov 2018)

Chromosome 17q gains are almost invariably present in high-risk neuroblastoma cases. Here, we perform an integrative epigenomics search for dosage-sensitive transcription factors on 17q marked by H3K27ac defined super-enhancers and identify TBX2 as top candidate gene. We show that TBX2 is a constituent of the recently established core regulatory circuitry in neuroblastoma with features of a cell identity transcription factor, driving proliferation through activation of p21-DREAM repressed FOXM1 target genes. Combined MYCN/TBX2 knockdown enforces cell growth arrest suggesting that TBX2 enhances MYCN sustained activation of FOXM1 targets. Targeting transcriptional addiction by combined CDK7 and BET bromodomain inhibition shows synergistic effects on cell viability with strong repressive effects on CRC gene expression and p53 pathway response as well as several genes implicated in transcriptional regulation. In conclusion, we provide insight into the role of the TBX2 CRC gene in transcriptional dependency of neuroblastoma cells warranting clinical trials using BET and CDK7 inhibitors.]]>
Wed, 31 Dec 1969 19:00:00 EST
Long noncoding RNAs: A new player in the prevention and treatment of diabetic cardiomyopathy? Ma C, Luo H, Liu B, Li F, Tschöpe C, Fa X
Diabetes Metab Res Rev (11 2018)

Diabetic cardiomyopathy (DCM) can cause extensive necrosis of the heart muscle by metabolic disorders and microangiopathy, with subclinical cardiac dysfunction, and eventually progress to heart failure, arrhythmia, and cardiogenic shock; severe patients may even die suddenly. Long noncoding RNAs (lncRNAs) are a class of nonprotein-coding RNAs longer than 200 nucleotides. They have critical roles in various biological processes, including gene expression regulation, genomic imprinting, nuclear-cytoplasmic trafficking, RNA splicing, and translational control. Recent studies indicated that lncRNAs extensively participate in the development of diverse cardiac diseases, such as cardiac ischaemia, hypertrophy, and heart failure. Little is known about lncRNA in DCM. In this review, we summarize the current literature on lncRNAs in DCM studies, aiming to provide new methods for DCM's future prevention and treatment strategies.]]>
Wed, 31 Dec 1969 19:00:00 EST
ChIP-Atlas: a data-mining suite powered by full integration of public ChIP-seq data. Oki S, Ohta T, Shioi G, Hatanaka H, Ogasawara O, Okuda Y, Kawaji H, Nakaki R, Sese J, Meno C
EMBO Rep (Nov 2018)

We have fully integrated public chromatin chromatin immunoprecipitation sequencing (ChIP-seq) and DNase-seq data ( > 70,000) derived from six representative model organisms (human, mouse, rat, fruit fly, nematode, and budding yeast), and have devised a data-mining platform-designated ChIP-Atlas (http://chip-atlas.org). ChIP-Atlas is able to show alignment and peak-call results for all public ChIP-seq and DNase-seq data archived in the NCBI Sequence Read Archive (SRA), which encompasses data derived from GEO, ArrayExpress, DDBJ, ENCODE, Roadmap Epigenomics, and the scientific literature. All peak-call data are integrated to visualize multiple histone modifications and binding sites of transcriptional regulators (TRs) at given genomic loci. The integrated data can be further analyzed to show TR-gene and TR-TR interactions, as well as to examine enrichment of protein binding for given multiple genomic coordinates or gene names. ChIP-Atlas is superior to other platforms in terms of data number and functionality for data mining across thousands of ChIP-seq experiments, and it provides insight into gene regulatory networks and epigenetic mechanisms.]]>
Wed, 31 Dec 1969 19:00:00 EST
Polymorphic Imprinting of SLC38A4 Gene in Bovine Placenta. Xu D, Zhang C, Li J, Wang G, Chen W, Li D, Li S
Biochem Genet (Dec 2018)

Imprinted genes are characterized by monoallelic expression that is dependent on parental origin. Comparative analysis of imprinted genes between species is a powerful tool for understanding the biological significance of genomic imprinting. The slc38a4 gene encodes a neutral amino acid transporter and is identified as imprinted in mice. In this study, the imprinting status of SLC38A4 was assessed in bovine adult tissues and placenta using a polymorphism-based approach. Results indicate that SLC38A4 is not imprinted in eight adult bovine tissues including heart, liver, spleen, lung, kidney, muscle, fat, and brain. It was interesting to note that SLC38A4 showed polymorphic status in five heterogeneous placentas, with three exhibiting paternal monoallelic expression and two exhibiting biallelic expression. Monoallelic expression of imprinted genes is generally associated with allele-specific differentially methylation regions (DMRs) of CpG islands (CGIs)-encompassed promoter; therefore, the DNA methylation statuses of three CGIs in the SLC38A4 promoter and exon 1 region were tested in three placentas (two exhibiting paternal monoallelic and one showing biallelic expression of SLC38A4) and their corresponding paternal sperms. Unexpectedly, extreme hypomethylation (< 3%) of the DNA was observed in all the three detected placentas and their corresponding paternal sperms. The absence of DMR in bovine SLC38A4 promoter region implied that DNA methylation of these three CGIs does not directly or indirectly affect the polymorphic imprinting of SLC38A4 in bovine placenta. This suggested other epigenetic features other than DNA methylation are needed in regulating the imprinting of bovine SLC38A4, which is different from that of mouse with respect to a DMR existence at the mouse's slc38a4 promoter region. Although further work is needed, this first characterization of polymorphic imprinting status of SLC38A4 in cattle placenta provides valuable information on investigating the genomic imprinting phenomenon itself.]]>
Wed, 31 Dec 1969 19:00:00 EST
Prognostic models in primary biliary cholangitis. Cristoferi L, Nardi A, Ronca V, Invernizzi P, Mells G, Carbone M
J Autoimmun (Nov 2018)

Risk prediction modelling is important to better understand the determinants of the course and outcome of PBC and to inform the risk across the disease continuum in PBC enabling risk-stratified follow-up care and personalised therapy. Current prognostic models in PBC are based on treatment response to ursodeoxycholic acid because of the well-established relationship between alkaline phosphatase on treatment and long-term outcome. In addition, serum alkaline phosphatase correlates with ductular reaction and biliary metaplasia, which are hallmark of biliary injury. Considering the waiting time for treatment failure in high-risk patients is not inconsequential, efforts are focused on bringing forward risk stratification at diagnosis by predicting treatment response at onset. There is a need for better prognostic variables that are central to the disease process. We should take an integrative approach that incorporates multiple layers of information including genetic and environmental influences, host characteristics, clinical data, and molecular alterations for risk assessments. Biomarker discovery has an accelerated pace taking advantage of the emergence of large-scale omics platforms (genomics, epigenomics, transcriptomics, proteomics, metabolomics, and others) and whole-genome sequencing. In the digital era, applications of artificial intelligence, such as machine learning, can support the computing power required to analyse the vast amount of data produced by omics. The information is then used for the development of personalised risk prediction models that through clinical trials and hopefully industry partnerships can guide risk management strategies. We are facing an unprecedented opportunity for the integration of molecular diagnostics into the clinic, which promotes progress toward the personalised management of patients with PBC.]]>
Wed, 31 Dec 1969 19:00:00 EST
Mice from Same-Sex Parents: CRISPRing Out the Barriers for Unisexual Reproduction. Sagi I, Bar S, Benvenisty N
Cell Stem Cell (Nov 2018)

Genomic imprinting results in the molecular and functional inequality of maternal and paternal alleles, precluding mammalian unisexual development. In this issue of Cell Stem Cell, Li et al. (2018) employ sophisticated manipulations of gametes and engineered haploid embryonic stem cells to successfully generate both all-maternal and all-paternal mice, effectively overcoming the roadblocks of imprinting.]]>
Wed, 31 Dec 1969 19:00:00 EST
Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression. Schmiedel BJ, Singh D, Madrigal A, Valdovino-Gonzalez AG, White BM, Zapardiel-Gonzalo J, Ha B, Altay G, Greenbaum JA, McVicker G, Seumois G, Rao A, Kronenberg M, Peters B, Vijayanand P
Cell (Nov 2018)

While many genetic variants have been associated with risk for human diseases, how these variants affect gene expression in various cell types remains largely unknown. To address this gap, the DICE (database of immune cell expression, expression quantitative trait loci [eQTLs], and epigenomics) project was established. Considering all human immune cell types and conditions studied, we identified cis-eQTLs for a total of 12,254 unique genes, which represent 61% of all protein-coding genes expressed in these cell types. Strikingly, a large fraction (41%) of these genes showed a strong cis-association with genotype only in a single cell type. We also found that biological sex is associated with major differences in immune cell gene expression in a highly cell-specific manner. These datasets will help reveal the effects of disease risk-associated genetic polymorphisms on specific immune cell types, providing mechanistic insights into how they might influence pathogenesis (https://dice-database.org).]]>
Wed, 31 Dec 1969 19:00:00 EST
Development and Functional Modulation of Regulatory T Cells by Transcription Factors and Epigenetics. Ito M, Iizuka-Koga M, Ando M, Yoshimura A
Cornea (Nov 2018)

Regulatory T cells (Tregs) are essential for the maintenance of immune homeostasis. Studies of Treg are not only necessary for understanding the mechanism of immune homeostasis but also extremely useful for the development of treatments of various immune diseases. Forkhead box P3 (Foxp3) was identified as the master gene responsible for the immune-suppressing activity of Tregs. The promoter region and several intronic enhancers, designated conserved noncoding sequence (CNS) 0, 1, 2, and 3, at the Foxp3 gene locus have important roles in Foxp3 expression and Treg development. We demonstrated that transcription factors Nr4a and Smad2/3 are required for development of thymic Tregs and induced Tregs, respectively. In addition to transcription factors, Treg-specific DNA demethylation has been shown to be important for Treg stability. In particular, DNA demethylation of CNS2 was implicated in Treg stability, and members of the ten-eleven translocation family of demethylation factors were recently demonstrated to have important roles in 5'-C-phosphate-G-3' demethylation at CNS2. This article summarizes recent findings regarding the roles of transcription factors and epigenetic modifications in the differentiation, maintenance, and function of Tregs. This review will facilitate clinical application of Tregs to diseases in the field of ophthalmology, including uveitis and age-related macular degeneration.]]>
Wed, 31 Dec 1969 19:00:00 EST
Intersexual conflict over seed size is stronger in more outcrossed populations of a mixed-mating plant. Raunsgard A, Opedal Ã˜H, Ekrem RK, Wright J, Bolstad GH, Armbruster WS, Pélabon C
Proc Natl Acad Sci U S A (Nov 2018)

In polyandrous species, fathers benefit from attracting greater maternal investment toward their offspring at the expense of the offspring of other males, while mothers should usually allocate resources equally among offspring. This conflict can lead to an evolutionary arms race between the sexes, manifested through antagonistic genes whose expression in offspring depends upon the parent of origin. The arms race may involve an increase in the strength of maternally versus paternally derived alleles engaged in a "tug of war" over maternal provisioning or repeated "recognition-avoidance" coevolution where growth-enhancing paternally derived alleles evolve to escape recognition by maternal genes targeted to suppress their effect. Here, we develop predictions to distinguish between these two mechanisms when considering crosses among populations that have reached different equilibria in this intersexual arms race. We test these predictions using crosses within and among populations of (Euphorbiaceae) that presumably have experienced different intensities of intersexual conflict, as inferred from their historical differences in mating system. In crosses where the paternal population was more outcrossed than the maternal population, hybrid seeds were larger than those normally produced in the maternal population, whereas when the maternal population was more outcrossed, hybrid seeds were smaller than normal. These results confirm the importance of mating systems in determining the intensity of intersexual conflict over maternal investment and provide strong support for a tug-of-war mechanism operating in this conflict. They also yield clear predictions for the fitness consequences of gene flow among populations with different mating histories.]]>
Wed, 31 Dec 1969 19:00:00 EST
Isolating mitotic and meiotic germ cells from male mice by developmental synchronization, staging, and sorting. Romer KA, de Rooij DG, Kojima ML, Page DC
Dev Biol (Nov 2018)

Isolating discrete populations of germ cells from the mouse testis is challenging, because the adult testis contains germ cells at every step of spermatogenesis, in addition to somatic cells. We present a novel method for isolating precise, high-purity populations of male germ cells. We first synchronize germ cell development in vivo by manipulating retinoic acid metabolism, and perform histological staging to verify synchronization. We use fluorescence-activated cell sorting to separate the synchronized differentiating germ cells from contaminating somatic cells and undifferentiated spermatogonia. We achieve ~90% purity at each step of development from undifferentiated spermatogonia through late meiotic prophase. Utilizing this "3 S" method (synchronize, stage, and sort), we can separate germ cell types that were previously challenging or impossible to distinguish, with sufficient yield for epigenetic and biochemical studies. 3 S expands the toolkit of germ cell sorting methods, and should facilitate detailed characterization of molecular and biochemical changes that occur during the mitotic and meiotic phases of spermatogenesis.]]>
Wed, 31 Dec 1969 19:00:00 EST
Longitudinal personal DNA methylome dynamics in a human with a chronic condition. Chen R, Xia L, Tu K, Duan M, Kukurba K, Li-Pook-Than J, Xie D, Snyder M
Nat Med (Nov 2018)

Epigenomics regulates gene expression and is as important as genomics in precision personal health, as it is heavily influenced by environment and lifestyle. We profiled whole-genome DNA methylation and the corresponding transcriptome of peripheral blood mononuclear cells collected from a human volunteer over a period of 36 months, generating 28 methylome and 57 transcriptome datasets. We found that DNA methylomic changes are associated with infrequent glucose level alteration, whereas the transcriptome underwent dynamic changes during events such as viral infections. Most DNA meta-methylome changes occurred 80-90 days before clinically detectable glucose elevation. Analysis of the deep personal methylome dataset revealed an unprecedented number of allelic differentially methylated regions that remain stable longitudinally and are preferentially associated with allele-specific gene regulation. Our results revealed that changes in different types of 'omics' data associate with different physiological aspects of this individual: DNA methylation with chronic conditions and transcriptome with acute events.]]>
Wed, 31 Dec 1969 19:00:00 EST
Alzheimer's disease DNA methylome of pyramidal layers in frontal cortex: laser-assisted microdissection study. Hernández HG, Sandoval-Hernández AG, Garrido-Gil P, Labandeira-Garcia JL, Zelaya MV, Bayon GF, Fernández AF, Fraga MF, Arboleda G, Arboleda H
Epigenomics (Nov 2018)

To study DNA methylation patterns of cortical pyramidal layers susceptible to late-onset Alzheimer's disease (LOAD) neurodegeneration.]]>
Wed, 31 Dec 1969 19:00:00 EST
Combinatorial regulation of hepatic cytoplasmic signaling and nuclear transcriptional events by the OGT/REV-ERBα complex. Berthier A, Vinod M, Porez G, Steenackers A, Alexandre J, Yamakawa N, Gheeraert C, Ploton M, Maréchal X, Dubois-Chevalier J, Hovasse A, Schaeffer-Reiss C, Cianférani S, Rolando C, Bray F, Duez H, Eeckhoute J, Lefebvre T, Staels B, Lefebvre P
Proc Natl Acad Sci U S A (Nov 2018)

The nuclear receptor REV-ERBα integrates the circadian clock with hepatic glucose and lipid metabolism by nucleating transcriptional comodulators at genomic regulatory regions. An interactomic approach identified O-GlcNAc transferase (OGT) as a REV-ERBα-interacting protein. By shielding cytoplasmic OGT from proteasomal degradation and favoring OGT activity in the nucleus, REV-ERBα cyclically increased O-GlcNAcylation of multiple cytoplasmic and nuclear proteins as a function of its rhythmically regulated expression, while REV-ERBα ligands mostly affected cytoplasmic OGT activity. We illustrate this finding by showing that REV-ERBα controls OGT-dependent activities of the cytoplasmic protein kinase AKT, an essential relay in insulin signaling, and of ten-of-eleven translocation (TET) enzymes in the nucleus. AKT phosphorylation was inversely correlated to REV-ERBα expression. REV-ERBα enhanced TET activity and DNA hydroxymethylated cytosine (5hmC) levels in the vicinity of REV-ERBα genomic binding sites. As an example, we show that the REV-ERBα/OGT complex modulates gene expression throughout the fasting/feeding periods by first repressing AKT phosphorylation and by epigenomically priming the promoter for a further rapid response to insulin. Conclusion: REV-ERBα regulates cytoplasmic and nuclear OGT-controlled processes that integrate at the hepatic locus to control basal and insulin-induced expression of the temporally and nutritionally regulated lipogenic transcript.]]>
Wed, 31 Dec 1969 19:00:00 EST
Epigenetic and transcriptional control of chickpea WRKY40 promoter activity under Fusarium stress and its heterologous expression in Arabidopsis leads to enhanced resistance against bacterial pathogen. Chakraborty J, Ghosh P, Sen S, Das S
Plant Sci (Nov 2018)

Promoters of many defense related genes are enriched with W-box elements serving as binding sites for plant specific WRKY transcription factors. In this study, expression of WRKY40 transcription factor was analyzed in two contrasting susceptible (JG62) and resistant (WR315) genotypes of chickpea infected with Foc1. The resistant plants showed up-regulation of WRKY40 under Fusarium stress, whereas in susceptible plants WRKY40 expression was absent. Additionally, global changes in the histone modification patterns were studied in above two chickpea genotypes by immunoblotting and real-time PCR analyses under control and Fusarium infected conditions. Notably, region specific Histone 3 lysine 9 acetylation, a positive marker of transcription gets enriched at WRKY40 promoter during resistant interaction with Foc1. H3K9 Ac is less enriched at WRKY40 promoter in Foc1 infected susceptible plants. WRKY40 promoter activity was induced by jasmonic acid and pathogen treatment, while salicylic acid failed to stimulate such activity. Moreover, WRKY40 was found to bind to its own promoter and auto-regulates its activity. The present study also showed that heterologous over-expression of chickpea WRKY40 triggers defense response in Arabidopsis against Pseudomonas syringae. Overall, we present epigenetic and transcriptional control of WRKY40 in chickpea under Fusarium stress and its immunomodulatory role is tested in Arabidopsis.]]>
Wed, 31 Dec 1969 19:00:00 EST