'; ?> 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, 31 Mar 2020 13:48:49 EDT Tue, 31 Mar 2020 13:48:49 EDT jirtle@radonc.duke.edu james001@jirtle.com Identification of a Plasma MicroRNA Profile Associated With Venous Thrombosis. Rodriguez-Rius A, Lopez S, Martinez-Perez A, Souto JC, Soria JM
Arterioscler Thromb Vasc Biol (Mar 2020)

Venous thrombosis (VT) is a complex condition with a highly heritable genetic component that predisposes one to its development. Certain microRNAs (miRNAs) might be used as biomarkers of VT, but few studies have examined miRNA expression in this respect. The aim of the present work was to identify a plasma miRNA profile associated with VT. Approach and Results: miRNAs were analyzed by qPCR in plasma samples from members of the GAIT-2 (Genetic Analysis of Idiopathic Thrombophilia 2) population (n=935). A discovery phase involving the screening of 752 miRNAs from a subset of 104 GAIT-2 subjects was followed by an internal validation phase in which the selected miRNAs were quantified in the whole GAIT-2 population. In the discovery phase, 16 miRNAs were selected, including 9 associated with VT and 7 that correlated with an intermediate phenotype of VT. In the next phase, 4 miRNAs were validated as differentially expressed (false discovery rate, <0.1) in VT: hsa-miR-126-3p, hsa-miR-885-5p, hsa-miR-194-5p, and hsa-miR-192-5p. The 4 miRNAs each returned a significant (<0.05) odds ratio for VT (range of 1.3-1.8). A risk model including the 4 miRNAs, age, and sex returned an area under the receiver operating characteristic curve of 0.77. Moreover, all 4 miRNAs showed significant correlations with intermediate phenotypes of VT (eg, protein S and factor VII). The targets of the miRNAs in the blood coagulation pathway and their interactions are also discussed.]]>
Wed, 31 Dec 1969 19:00:00 EST
Syndromic Disorders Caused by Disturbed Human Imprinting Carli D, Riberi E, Ferrero GB, Mussa A
J Clin Res Pediatr Endocrinol (03 2020)

Imprinting disorders are a group of congenital diseases caused by dysregulation of genomic imprinting, affecting prenatal and postnatal growth, neurocognitive development, metabolism and cancer predisposition. Aberrant expression of imprinted genes can be achieved through different mechanisms, classified into epigenetic - if not involving DNA sequence change - or genetic in the case of altered genomic sequence. Despite the underlying mechanism, the phenotype depends on the parental allele affected and opposite phenotypes may result depending on the involvement of the maternal or the paternal chromosome. Imprinting disorders are largely underdiagnosed because of the broad range of clinical signs, the overlap of presentation among different disorders, the presence of mild phenotypes, the mitigation of the phenotype with age and the limited availability of molecular techniques employed for diagnosis. This review briefly illustrates the currently known human imprinting disorders, highlighting endocrinological aspects of pediatric interest.]]>
Wed, 31 Dec 1969 19:00:00 EST
Histone acetylation together with DNA demethylation empowers higher plasticity in adipocytes to differentiate into osteoblasts. Cho YD, Kim BS, Kim WJ, Kim HJ, Baek JH, Woo KM, Seol YJ, Ku Y, Ryoo HM
Gene (Apr 2020)

Bone regeneration has been a challenge for both researchers and clinicians. In the field of tissue engineering, much effort has been made to identify cell sources including stem cells. The present study aimed to induce trans-differentiation from adipocytes to osteoblasts using epigenetic modifiers; 5-aza-dC and/or trichostatin-A (TSA). 3 T3-L1 preadipocytes were treated with TSA (100 nM) and then with Wnt3a (50 ng/ml). Microscopic observation showed trans-differentiated cell morphology. Methylation-specific PCR and immunoblotting were performed to analyze the DNA methylation and histone acetylation patterns. The gene expression was determined by real-time PCR. Based on these in vitro experiments, in vivo mouse experiments supplemented the possibility of trans-differentiation by epigenetic modification. TSA induced the acetylation of lysine9 on histone H3, and a sequential Wnt3a treatment stimulated the expression of bone marker genes in adipocytes, suppressing adipogenesis and stimulating osteogenesis. Furthermore, TSA induced DNA hypomethylation, and a combined treatment with TSA and 5-aza-dC showed a synergistic effect in epigenetic modifications. The number of adipocytes and DNA methylation patterns of old (15 months) and young (6 weeks) mice were significantly different, and TSA and sequential Wnt3a treatments increased bone formation in the old mice. Collectively, our results confirmed cell trans-differentiation via epigenetic modifications and osteogenic signaling from adipocytes to osteoblasts for the bone regeneration in vitro and in vivo, and indicated that histone acetylation could induce DNA hypomethylation, enhancing the chance of trans-differentiation.]]>
Wed, 31 Dec 1969 19:00:00 EST
Common genetic variation in the Angelman syndrome imprinting centre affects the imprinting of chromosome 15. Beygo J, Grosser C, Kaya S, Mertel C, Buiting K, Horsthemke B
Eur J Hum Genet (Mar 2020)

Angelman syndrome (AS) is a rare neurogenetic imprinting disorder caused by the loss of function of UBE3A. In ~3-5% of AS patients, the disease is due to an imprinting defect (ID). These patients lack DNA methylation of the maternal SNRPN promotor so that a large SNRPN sense/UBE3A antisense transcript (SNHG14) is expressed, which silences UBE3A. In very rare cases, the ID is caused by a deletion of the AS imprinting centre (AS-IC). To search for sequence alterations, we sequenced this region in 168 patients without an AS-IC deletion, but did not detect any sequence alteration. However, the AS-IC harbours six common variants (five single nucleotide variants and one TATG insertion/deletion variant), which constitute five common haplotypes. To determine if any of these haplotypes is associated with an increased risk for an ID, we investigated 119 informative AS-ID trios with the transmission disequilibrium test, which is a family-based association test that measures the over-transmission of an allele or haplotype from heterozygous parents to affected offspring. By this we observed maternal over-transmission of haplotype H-AS3 (p = 0.0073). Interestingly, H-AS3 is the only haplotype that includes the TATG deletion allele. We conclude that this haplotype and possibly the TATG deletion, which removes a SOX2 binding site, increases the risk for a maternal ID and AS. Our data strengthen the notion that the AS-IC is important for establishing and/or maintaining DNA methylation at the SNRPN promotor and show that common genetic variation can affect genomic imprinting.]]>
Wed, 31 Dec 1969 19:00:00 EST
Childhood asthma in the new omics era: challenges and perspectives. Golebski K, Kabesch M, Melén E, Potočnik U, van Drunen CM, Reinarts S, Maitland-van der Zee AH, Vijverberg SJH,  
Curr Opin Allergy Clin Immunol (Apr 2020)

Childhood asthma is a heterogeneous inflammatory disease comprising different phenotypes and endotypes and, particularly in its severe forms, has a large impact on the quality-of-life of patients and caregivers. The application of advanced omics technologies provides useful insights into underlying asthma endotypes and may provide potential clinical biomarkers to guide treatment and move towards a precision medicine approach.]]>
Wed, 31 Dec 1969 19:00:00 EST
A Susceptibility Locus on Chromosome 13 Profoundly Impacts the Stability of Genomic Imprinting in Mouse Pluripotent Stem Cells. Swanzey E, McNamara TF, Apostolou E, Tahiliani M, Stadtfeld M
Cell Rep (Mar 2020)

Cultured pluripotent cells accumulate detrimental chromatin alterations, including DNA methylation changes at imprinted genes known as loss of imprinting (LOI). Although the occurrence of LOI is considered a stochastic phenomenon, here we document a genetic determinant that segregates mouse pluripotent cells into stable and unstable cell lines. Unstable lines exhibit hypermethylation at Dlk1-Dio3 and other imprinted loci, in addition to impaired developmental potential. Stimulation of demethylases by ascorbic acid prevents LOI and loss of developmental potential. Susceptibility to LOI greatly differs between commonly used mouse strains, which we use to map a causal region on chromosome 13 with quantitative trait locus (QTL) analysis. Our observations identify a strong genetic determinant of locus-specific chromatin abnormalities in pluripotent cells and provide a non-invasive way to suppress them. This highlights the importance of considering genetics in conjunction with culture conditions for assuring the quality of pluripotent cells for biomedical applications.]]>
Wed, 31 Dec 1969 19:00:00 EST
High polygenic burden is associated with blood DNA methylation changes in individuals with suicidal behavior. Cabrera-Mendoza B, Martínez-Magaña JJ, Genis-Mendoza AD, Sarmiento E, Ruíz-Ramos D, Tovilla-Zárate CA, González-Castro TB, Juárez-Rojop IE, García-de la Cruz DD, López-Armenta M, Real F, García-Dolores F, Flores G, Vázquez-Roque RA, Lanzagorta N, Escamilla M, Saucedo-Uribe E, Rodríguez-Mayoral O, Jiménez-Genchi J, Castañeda-González C, Roche-Bergua A, Nicolini H
J Psychiatr Res (Apr 2020)

Suicidal behavior is result of the interaction of several contributors, including genetic and environmental factors. The integration of approaches considering the polygenic component of suicidal behavior, such as polygenic risk scores (PRS) and DNA methylation is promising for improving our understanding of the complex interplay between genetic and environmental factors in this behavior. The aim of this study was the evaluation of DNA methylation differences between individuals with high and low genetic burden for suicidality. The present study was divided into two phases. In the first phase, genotyping with the Psycharray chip was performed in a discovery sample of 568 Mexican individuals, of which 149 had suicidal behavior (64 individuals with suicidal ideation, 50 with suicide attempt and 35 with completed suicide). Then, a PRS analysis based on summary statistics from the Psychiatric Genomic Consortium was performed in the discovery sample. In a second phase, we evaluated DNA methylation differences between individuals with high and low genetic burden for suicidality in a sub-sample of the discovery sample (target sample) of 94 subjects. We identified 153 differentially methylated sites between individuals with low and high-PRS. Among genes mapped to differentially methylated sites, we found genes involved in neurodevelopment (CHD7, RFX4, KCNA1, PLCB1, PITX1, NUMBL) and ATP binding (KIF7, NUBP2, KIF6, ATP8B1, ATP11A, CLCN7, MYLK, MAP2K5). Our results suggest that genetic variants might increase the predisposition to epigenetic variations in genes involved in neurodevelopment. This study highlights the possible implication of polygenic burden in the alteration of epigenetic changes in suicidal behavior.]]>
Wed, 31 Dec 1969 19:00:00 EST
Bromodomain and extra-terminal domain (BET) proteins regulate melanocyte differentiation. Trivedi A, Mehrotra A, Baum CE, Lewis B, Basuroy T, Blomquist T, Trumbly R, Filipp FV, Setaluri V, de la Serna IL
Epigenetics Chromatin (Mar 2020)

Pharmacologic inhibition of bromodomain and extra-terminal (BET) proteins is currently being explored as a new therapeutic approach in cancer. Some studies have also implicated BET proteins as regulators of cell identity and differentiation through their interactions with lineage-specific factors. However, the role of BET proteins has not yet been investigated in melanocyte differentiation. Melanocyte inducing transcription factor (MITF) is the master regulator of melanocyte differentiation, essential for pigmentation and melanocyte survival. In this study, we tested the hypothesis that BET proteins regulate melanocyte differentiation through interactions with MITF.]]>
Wed, 31 Dec 1969 19:00:00 EST
Museum Epigenomics: Charting the Future by Unlocking the Past. Hahn EE, Grealy A, Alexander M, Holleley CE
Trends Ecol Evol (Apr 2020)

Epigenomic state preserved in museum specimens could be leveraged to provide unique insights into gene regulation trends associated with accelerating environmental change during the Anthropocene. We address the challenges facing museum epigenomics and propose a collaborative framework for researchers and curators to explore this new field.]]>
Wed, 31 Dec 1969 19:00:00 EST
Multi-omics analysis at epigenomics and transcriptomics levels reveals prognostic subtypes of lung squamous cell carcinoma. Xu Y, She Y, Li Y, Li H, Jia Z, Jiang G, Liang L, Duan L
Biomed Pharmacother (May 2020)

In this study, we identified prognostic biomarkers for lung squamous cell carcinoma (LUSC) by integrating multiple sets of DNA copy number variants (CNV) and methylation variant (MET) data, and performing qPCR and immunohistochemical identification. We examined the expression of CNV and MET in 368 LUSC patients. Gene expression associated with DNA copy number or DNA methylation was identified and four LUSC gene subtypes were defined based on these correlations. The prognosis overall survival (OS) of the iC1 subtype was significantly lower than that in the iC2 and iC4 subtypes. We assessed the immune scores of each subtype and found that the six immune cell scores of the iC3 subtype were significantly higher than the other subtypes (p < 0.01). Three genes associated with prognosis, NFE2L2, ASAH2, and RIMBP2, were identified by comparing the expression of CNV and MET in subtypes. Analysis of mutational differences between subtypes revealed a group of genes with significant mutations between the iC1 and iC4 subtypes. The number of mutations in the NFE2L2 gene in LUSC was significantly higher than that in other genes, and the gene was prognostic. The number of mutations was significantly higher in the best iC4 subtype than the iC1 subtype with the worst prognosis; the other two genes, ASAH2 and RIMBP2, were only found in the worst prognosis of the iC1 subtype. This comprehensive multi-omics analysis of genomics, epigenomics, and transcriptomics data provides new insights into the molecular mechanisms of LUSC and may be helpful in identifying biomolecular markers for early disease diagnosis.]]>
Wed, 31 Dec 1969 19:00:00 EST
Single-Cell Multi-omics and Its Prospective Application in Cancer Biology. Peng A, Mao X, Zhong J, Fan S, Hu Y
Proteomics (Mar 2020)

Recent years, the emergence of single-cell omics technologies, which can profile genomics, transcriptomics, epigenomics, and proteomics, has provided unprecedented insights into characteristics of cancer, enabling higher resolution and accuracy to decipher the cellular and molecular mechanisms relating to tumorigenesis, evolution, metastasis, and immune responses. Single-cell multi-omics technologies, which were developed based on the combination of multiple single-cell mono-omics technologies, could simultaneously analyze RNA expression, single nucleotide polymorphism, epigenetic modification, or protein abundance, enabling the in-depth understanding of gene expression regulatory mechanisms. In this review, we summarize the state-of-the-art single-cell multi-omics technologies and discuss the prospects of their application in cancer biology. This article is protected by copyright. All rights reserved.]]>
Wed, 31 Dec 1969 19:00:00 EST
Behavioral Effects of Neuronal, Parent-specific Commd1 Knockout in Mice. Chase KA, Mallari JE, Tan Y, Sittig L
Neuroscience (Mar 2020)

In this study we focused on gene expression and behavioral differences in mice with brain-specific Commd1 knockout. Commd1 is an imprinted gene with preferential maternal expression, residing within a larger genomic region previously found to affect sensorimotor gating. In this study, individuals harboring a conditional Commd1 mutant allele were bred with Syn1-Cre animals, paying special attention to the parent of origin of the Commd1 mutation. Analysis of mRNA levels of Commd1 and phenotypic tests, including the open field, sensorimotor gating, and the forced swim test, were conducted on offspring with either maternally or paternally derived Commd1 knockout. We found that measurable Commd1 mRNA knockout occurred only in the maternally derived line and affected stereotypy and depressive-like behavior without differences in total locomotion compared to controls. Interestingly, we found that maternal knockout animals exhibited decreased time swimming and increased time immobile when compared to maternal and paternal wild type, and paternal knockout animals. However, there were no differences in climbing behavior between genotypes. This study demonstrates an in vivo behavioral role for Commd1 for the first time and demonstrates the need for careful interpretation of experimental results involving Cre-based knockout systems.]]>
Wed, 31 Dec 1969 19:00:00 EST
Genomic Characterization of Endothelial Enhancers Reveals a Multifunctional Role for NR2F2 in Regulation of Arteriovenous Gene Expression. Sissaoui S, Yu J, Yan A, Li R, Yukselen O, Kucukural A, Zhu LJ, Lawson ND
Circ Res (Mar 2020)

Significant progress has revealed transcriptional inputs that underlie regulation of artery and vein endothelial cell fates. However, little is known concerning genome-wide regulation of this process. Therefore, such studies are warranted to address this gap.]]>
Wed, 31 Dec 1969 19:00:00 EST
Comparing genome-scale DNA methylation and CNV marks between adult human cultured ITGA6+ testicular cells and seminomas to assess in vitro genomic stability. Struijk RB, Dorssers LCJ, Henneman P, Rijlaarsdam MA, Venema A, Jongejan A, Mannens MMAM, Looijenga LHJ, Repping S, van Pelt AMM
PLoS One (2020)

Autologous transplantation of spermatogonial stem cells is a promising new avenue to restore fertility in infertile recipients. Expansion of the initial spermatogonial stem cell pool through cell culturing is a necessary step to obtain enough cells for effective repopulation of the testis after transplantation. Since in vitro propagation can lead to (epi-)genetic mutations and possibly malignant transformation of the starting cell population, we set out to investigate genome-wide DNA methylation status in uncultured and cultured primary testicular ITGA6+ sorted cells and compare them with germ cell tumor samples of the seminoma subtype. Seminomas displayed a severely global hypomethylated profile, including loss of genomic imprinting, which we did not detect in cultured primary testicular ITGA6+ cells. Differential methylation analysis revealed altered regulation of gamete formation and meiotic processes in cultured primary testicular ITGA6+ cells but not in seminomas. The pivotal POU5F1 marker was hypomethylated in seminomas but not in uncultured or cultured primary testicular ITGA6+ cells, which is reflected in the POU5F1 mRNA expression levels. Lastly, seminomas displayed a number of characteristic copy number variations that were not detectable in primary testicular ITGA6+ cells, either before or after culture. Together, the data show a distinct DNA methylation patterns in cultured primary testicular ITGA6+ cells that does not resemble the pattern found in seminomas, but also highlight the need for more sensitive methods to fully exclude the presence of malignant cells after culture and to further study the epigenetic events that take place during in vitro culture.]]>
Wed, 31 Dec 1969 19:00:00 EST
Paternally-biased gene expression follows kin-selected predictions in female honey bee embryos. Smith NMA, Yagound B, Remnant EJ, Foster CSP, Buchmann G, Allsopp MH, Kent CF, Zayed A, Rose SA, Lo K, Ashe A, Harpur BA, Beekman M, Oldroyd BP
Mol Ecol (Mar 2020)

The Kinship Theory of Genomic Imprinting (KTGI) posits that, in species where females mate with multiple males, there is selection for a male to enhance the reproductive success of his offspring at the expense of other males and his mating partner. Reciprocal crosses between honey bee subspecies show parent-of-origin effects for reproductive traits, suggesting that males modify the expression of genes related to female function in their female offspring. This effect is likely to be greater in the Cape honey bee (Apis mellifera capensis), because a male's daughters have the unique ability to produce female offspring that can develop into reproductive workers or the next queen without mating. We generated reciprocal crosses between Capensis and another subspecies and used RNA-seq to identify transcripts that are over- or under-expressed in the embryos, depending on the parental origin of the gene. As predicted, 21 genes showed expression bias towards the Capensis father's allele in colonies with a Capensis father, with no such bias in the reciprocal cross. A further six genes showed a consistent bias towards expression of the father's allele across all eight colonies examined, regardless of the direction of the cross. Consistent with predictions of the KTGI, six of the 21 genes are associated with female reproduction. No gene consistently showed over-expression of the maternal allele.]]>
Wed, 31 Dec 1969 19:00:00 EST
Transcriptomic and epigenomics atlas of myotubes reveals insight into the circadian control of metabolism and development. Altıntaş A, Laker RC, Garde C, Barrès R, Zierath JR
Epigenomics (Mar 2020)

Innate circadian rhythms are critical for optimal tissue-specific functions, including skeletal muscle, a major insulin-sensitive tissue responsible for glucose homeostasis. We determined whether transcriptional oscillations are associated with CpG methylation changes in skeletal muscle. We performed rhythmicity analysis on the transcriptome and CpG methylome of circadian synchronized myotubes. We identified several transcripts and CpG-sites displaying oscillatory behavior, which were enriched with GO terms related to metabolism and development. Oscillating CpG methylation was associated with rhythmic expression of 31 transcripts. Although circadian oscillations may be regulated by rhythmic DNA methylation, strong rhythmic associations between transcriptome and CpG methylation were not identified. This resource constitutes a transcriptomic/epigenomic atlas of skeletal muscle and regulation of circadian rhythms.]]>
Wed, 31 Dec 1969 19:00:00 EST
Potential role of genomic imprinted genes and brain developmental related genes in autism. Li J, Lin X, Wang M, Hu Y, Xue K, Gu S, Lv L, Huang S, Xie W
BMC Med Genomics (03 2020)

Autism is a complex disease involving both environmental and genetic factors. Recent efforts have implicated the correlation of genomic imprinting and brain development in autism, however the pathogenesis of autism is not completely clear. Here, we used bioinformatic tools to provide a comprehensive analysis of the autism-related genes, genomic imprinted genes and the spatially and temporally differentially expressed genes of human brain, aiming to explore the relationship between autism, brain development and genomic imprinting.]]>
Wed, 31 Dec 1969 19:00:00 EST
Imprinted genes in clinical exome sequencing: Review of 538 cases and exploration of mouse-human conservation in the identification of novel human disease loci. Bhoj EJ, Rajabi F, Baker SW, Santani A, Tan WH
Eur J Med Genet (Mar 2020)

Human imprinting disorders cause a range of dysmorphic and neurocognitive phenotypes, and they may elude traditional molecular diagnosis such exome sequencing. The discovery of novel disorders related to imprinted genes has lagged behind traditional Mendelian disorders because current diagnostic technology, especially unbiased testing, has limited utility in their discovery. To identify novel imprinting disorders, we reviewed data for every human gene hypothesized to be imprinted, identified each mouse ortholog, determined its imprinting status in the mouse, and analyzed its function in humans and mice. We identified 17 human genes that are imprinted in both humans and mice, and have functional data in mice or humans to suggest that dysregulated expression would lead to an abnormal phenotype in humans. These 17 genes, along with known imprinted genes, were preferentially flagged 538 clinical exome sequencing tests. The identified genes were: DIRAS3 [1p31.3], TP73 [1p36.32], SLC22A3 [6q25.3], GRB10 [7p12.1], DDC [7p12.2], MAGI2 [7q21.11], PEG10 [7q21.3], PPP1R9A [7q21.3], CALCR [7q21.3], DLGAP2 [8p23.3], GLIS3 [9p24.2], INPP5F [10q26.11], ANO1 [11q13.3], SLC38A4 [12q13.11], GATM [15q21.1], PEG3 [19q13.43], and NLRP2 [19q13.42]. In the 538 clinical cases, eight cases (1.7%) reported variants in a causative known imprinted gene. There were 367/758 variants (48.4%) in imprinted genes that were not known to cause disease, but none of those variants met the criteria for clinical reporting. Imprinted disorders play a significant role in human disease, and additional human imprinted disorders remain to be discovered. Therefore, evolutionary conservation is a potential tool to identify novel genes involved in human imprinting disorders and to identify them in clinical testing.]]>
Wed, 31 Dec 1969 19:00:00 EST
Long-Read Genome Sequencing and Assembly of : A Specialist Parasitoid. Khan S, Sowpati DT, Srinivasan A, Soujanya M, Mishra RK
G3 (Bethesda) (Mar 2020)

(Hymenoptera: Figitidae) is a specialist parasitoid of The - system has emerged as a suitable model for understanding several aspects of host-parasitoid biology. However, a good quality genome of the wasp counterpart was lacking. Here, we report a whole-genome assembly of to bring it in the scope of the applied and fundamental research on parasitoids with access to epigenomics and genome editing tools. The 375Mb draft genome has an N50 of 275Kb with 6315 scaffolds >500bp and encompasses >95% complete BUSCOs. Using a combination of and RNA-Seq based methods, 25259 protein-coding genes were predicted and 90% (22729) of them could be annotated with at least one function. We demonstrate the quality of the assembled genome by recapitulating the phylogenetic relationship of with other Hymenopterans. The key developmental regulators like Hox genes and sex determination genes are well conserved in , and so is the basic toolkit for epigenetic regulation. The search for epigenetic regulators has also revealed that genome possesses DNMT1 (maintenance DNA methyltransferase), DNMT2 (tRNA methyltransferase) but lacks the DNA methyltransferase (DNMT3). Also, the heterochromatin protein 1 family appears to have expanded as compared to other hymenopterans. The draft genome of (Lb17) will expedite the research on parasitoids. This genome resource and early indication of epigenetic aspects in its specialization make it an interesting system to address a variety of questions on host-parasitoid biology.]]>
Wed, 31 Dec 1969 19:00:00 EST
Blood DNA Methylation and Aging: A Cross-Sectional Analysis and Longitudinal Validation in the InCHIANTI Study. Tharakan R, Ubaida-Mohien C, Moore AZ, Hernandez D, Tanaka T, Ferrucci L
J Gerontol A Biol Sci Med Sci (Mar 2020)

Changes in DNA methylation have been found to be highly correlated with aging in humans, but causes or consequences of these changes are not understood. We characterized the DNA methylomes of several hundred people in the InCHIANTI study to identify DNA sites in which percent methylation was systematically different with age. Then, we tested the hypothesis that changes of percent methylation in the same DNA sites occur longitudinally for the same DNA sites in the same subjects. We identified six differentially methylated regions in which percent methylation showed robust longitudinal changes in the same direction. We then describe functions of the genes near these differentially methylated regions and their potential relationship with aging, noting that the genes appear to regulate metabolism or cell type specificity. The nature of transcription factor binding sites in the vicinity of these differentially methylated regions suggest that these age-associated methylation changes reflect modulation of two biological mechanisms: the polycomb repressive complex 2 (PRC2), a protein complex that trimethylates histone H3 on lysine 27 and the transcriptional repressor CTCF, both of which are regulators of chromatin architecture. These findings are consistent with the idea that changes in methylation with aging are of adaptive nature.]]>
Wed, 31 Dec 1969 19:00:00 EST