'; ?> 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, 24 May 2022 07:16:22 EDT Tue, 24 May 2022 07:16:22 EDT jirtle@radonc.duke.edu james001@jirtle.com Genome-wide DNA methylation profiling and exome sequencing resolved a long-time misdiagnosed case. Paparella A, Squeo GM, Di Venere E, Cardea E, Mazza T, Castellana S, Kerkhof J, McConkey H, Sadikovic B, Sinibaldi L, Digilio MC, Merla G
J Hum Genet (May 2022)

The search for aetiology of Mendelian disorders is traditionally based on the observation of clinical phenotypes and molecular screening of associated genes. However, a disease-specific diagnosis can be challenging. In this study we detail how the combinatorial genomic and epigenomic assessment allowed to find the underlying molecular event of a clinical case that remained misdiagnosed for years. The individual was referred as affected by an atypical form of Kabuki syndrome with a variant of uncertain significance in the KMT2D gene. However, significant inconsistencies with this diagnosis emerged upon familial segregation of the variant and after the clinical re-evaluation. Therefore, we applied an epigenomic strategy by studying the DNA methylation profile which resulted not consistent with the Kabuki syndrome episignature or with any other disorder-specific episignature described so far, providing strong evidence that the Kabuki syndrome diagnosis does not apply. This result led us to further investigate for epigenetic machinery diseases by using a multigene panel for chromatinopathies. Since this analysis yielded negative results, we applied a whole exome sequencing and identified a de novo pathogenic variant in the CTNNB1 gene associated to NEDSDV syndrome, a neurodevelopmental disorder characterized by intellectual disability and craniofacial anomalies. Based on molecular results and the updated clinical features, we confirmed the NEDSDV diagnosis. Our findings show that the combination of genomic and epigenomics strategies, along with a deeper analysis of clinical phenotype, may provide a significant improvement in the diagnostic protocols for rare genetic disorders and help resolve long-time misdiagnosed and unsolved case.]]>
Wed, 31 Dec 1969 19:00:00 EST
Epigenetic modifications at DMRs of imprinting genes in sperm of type 2 diabetic men. Jazayeri M, Eftekhari-Yazdi P, Sadighi Gilani MA, Sharafi M, Shahverdi A
Zygote (May 2022)

High rates of infertility in type 2 diabetic (T2DM) men have led to attempts to understand the mechanisms involved in this process. This condition can be investigated from at least two aspects, namely sperm quality indices and epigenetic alterations. Epigenetics science encompasses the phenomena that can lead to inherited changes independently of the genetics. This study has been performed to test the hypothesis of the relationship between T2DM and the epigenetic profile of the sperm, as well as sperm quality indices. This research included 42 individuals referred to the infertility clinic of Royan Institute, Iran in 2019-2021. The study subjects were assigned to three groups: normozoospermic non-diabetic (control), normozoospermic diabetic (DN) and non-normozoospermic diabetic (D.Non-N). Sperm DNA fragmentation was evaluated using the sperm chromatin structure assay technique. The global methylation level was examined using 5-methyl cytosine antibody and the methylation status in differentially methylated regions of H19, MEST, and SNRPN was assessed using the methylation-sensitive high-resolution melting technique. The results showed that the sperm global methylation in spermatozoa of D.Non-N group was significantly reduced compared with the other two groups (P < 0.05). The MEST and H19 genes were hypomethylated in the spermatozoa of D.Non-N individuals, but the difference level was not significant for MEST. The SNRPN gene was significantly hypermethylated in these individuals (P < 0.05). The results of this study suggest that T2DM alters the methylation profile and epigenetic programming in spermatozoa of humans and that these methylation changes may ultimately influence the fertility status of men with diabetes.]]>
Wed, 31 Dec 1969 19:00:00 EST
Fish metabolome from sub-urban lakes of the Paris area (France) and potential influence of noxious metabolites produced by cyanobacteria. Marie B, Gallet A
Chemosphere (Jun 2022)

The recent democratization of high-throughput molecular phenotyping allows the rapid expansion of promising untargeted multi-dimensional approaches (e.g. epigenomics, transcriptomics, proteomics, and/or metabolomics). Indeed, these emerging omics tools, processed for ecologically relevant species, may present innovative perspectives for environmental assessments, that could provide early warning of eco(toxico)logical impairments. In a previous pilot study (Sotton et al., Chemosphere 2019), we explore by H NMR the bio-indicative potential of metabolomics analyses on the liver of 2 sentinel fish species (Perca fluviatilis and Lepomis gibbosus) collected in 8 water bodies of the peri-urban Paris' area (France). In the present study, we further investigate on the same samples the high potential of high-throughput UHPLC-HRMS/MS analyses. We show that the LC-MS metabolome investigation allows a clear separation of individuals according to the species, but also according to their respective sampling lakes. Interestingly, similar variations of Perca and Lepomis metabolomes occur locally indicating that site-specific environmental constraints drive the metabolome variations which seem to be influenced by the production of noxious molecules by cyanobacterial blooms in certain lakes. Thus, the development of such reliable environmental metabolomics approaches appears to constitute an innovative bio-indicative tool for the assessment of ecological stress, such as toxigenic cyanobacterial blooms, and aim at being further follow up.]]>
Wed, 31 Dec 1969 19:00:00 EST
Machine learning: its challenges and opportunities in plant system biology. Hesami M, Alizadeh M, Jones AMP, Torkamaneh D
Appl Microbiol Biotechnol (May 2022)

Sequencing technologies are evolving at a rapid pace, enabling the generation of massive amounts of data in multiple dimensions (e.g., genomics, epigenomics, transcriptomic, metabolomics, proteomics, and single-cell omics) in plants. To provide comprehensive insights into the complexity of plant biological systems, it is important to integrate different omics datasets. Although recent advances in computational analytical pipelines have enabled efficient and high-quality exploration and exploitation of single omics data, the integration of multidimensional, heterogenous, and large datasets (i.e., multi-omics) remains a challenge. In this regard, machine learning (ML) offers promising approaches to integrate large datasets and to recognize fine-grained patterns and relationships. Nevertheless, they require rigorous optimizations to process multi-omics-derived datasets. In this review, we discuss the main concepts of machine learning as well as the key challenges and solutions related to the big data derived from plant system biology. We also provide in-depth insight into the principles of data integration using ML, as well as challenges and opportunities in different contexts including multi-omics, single-cell omics, protein function, and protein-protein interaction. KEY POINTS: • The key challenges and solutions related to the big data derived from plant system biology have been highlighted. • Different methods of data integration have been discussed. • Challenges and opportunities of the application of machine learning in plant system biology have been highlighted and discussed.]]>
Wed, 31 Dec 1969 19:00:00 EST
Integrating DNA Methylation Measures of Biological Aging into Social Determinants of Health Research. Raffington L, Belsky DW
Curr Environ Health Rep (Jun 2022)

Acceleration of biological processes of aging is hypothesized to drive excess morbidity and mortality in socially disadvantaged populations. DNA methylation measures of biological aging provide tools for testing this hypothesis.]]>
Wed, 31 Dec 1969 19:00:00 EST
Targeting DNA Methylation as an Epigenetic Leukocyte Counting Tool. Pittella-Silva F
Clin Chem (May 2022)

Wed, 31 Dec 1969 19:00:00 EST
'Omics in environmental epidemiological studies of chemical exposures: A systematic evidence map. Kim S, Hollinger H, Radke EG
Environ Int (Jun 2022)

Systematic evidence maps are increasingly used to develop chemical risk assessments. These maps can provide an overview of available studies and relevant study information to be used for various research objectives and applications. Environmental epidemiological studies that examine the impact of chemical exposures on various 'omic profiles in human populations provide relevant mechanistic information and can be used for benchmark dose modeling to derive potential human health reference values.]]>
Wed, 31 Dec 1969 19:00:00 EST
H3-K27M-mutant nucleosomes interact with MLL1 to shape the glioma epigenetic landscape. Furth N, Algranati D, Dassa B, Beresh O, Fedyuk V, Morris N, Kasper LH, Jones D, Monje M, Baker SJ, Shema E
Cell Rep (May 2022)

Cancer-associated mutations in genes encoding histones dramatically reshape chromatin and support tumorigenesis. Lysine to methionine substitution of residue 27 on histone H3 (K27M) is a driver mutation in high-grade pediatric gliomas, known to abrogate polycomb repressive complex 2 (PRC2) activity. We applied single-molecule systems to image individual nucleosomes and delineate the combinatorial epigenetic patterns associated with H3-K27M expression. We found that chromatin marks on H3-K27M-mutant nucleosomes are dictated both by their incorporation preferences and by intrinsic properties of the mutation. Mutant nucleosomes not only preferentially bind PRC2 but also directly interact with MLL1, leading to genome-wide redistribution of H3K4me3. H3-K27M-mediated deregulation of repressive and active chromatin marks leads to unbalanced "bivalent" chromatin, which may support a poorly differentiated cellular state. This study provides evidence for a direct effect of H3-K27M oncohistone on the MLL1-H3K4me3 pathway and highlights the capability of single-molecule tools to reveal mechanisms of chromatin deregulation in cancer.]]>
Wed, 31 Dec 1969 19:00:00 EST
Pan-tissue methylation aging clock: Recalibrated and a method to analyze and interpret the selected features. Vijayakumar KA, Cho GW
Mech Ageing Dev (Jun 2022)

The abundance of the biological data and the rapid evolution of the newer machine learning technologies have increased the epigenetics research in the last decade. This has enhanced the ability to measure the biological age of humans and different organisms via their omics data. DNA methylation array data are commonly used in the prediction of methylation age. Horvath clock has been adopted in various aging studies as a DNA methylation age predicting clock due to its higher accuracy and multi tissue prediction potential. In the current study, we have developed a pan tissue methylation-aging clock by using the publicly available illumina 450k and EPIC array methylation datasets. In doing that, we developed a highly accurate epigenetic clock, which predicts the age of multiple tissues with higher accuracy. We have also analyzed the selected probes for their biological relevance. Upon analyzing the selected features further, we found out evidences, which support the Antagonistic pleiotropy theory of aging.]]>
Wed, 31 Dec 1969 19:00:00 EST
A patient with multilocus imprinting disturbance involving hypomethylation at 11p15 and 14q32, and phenotypic features of Beckwith-Wiedemann and Temple syndromes. Grosvenor SE, Davies JH, Lever M, Sillibourne J, Mackay DJG, Temple IK
Am J Med Genet A (Jun 2022)

Beckwith-Wiedemann syndrome (BWS) and Temple syndrome (TS) are classical imprinting disorders (IDs) with nonconfluent clinical features. We report here on a patient with clinical features of both syndromes, in whom epimutations were found at the BWS and TS imprinted regions, consistent with multilocus imprinting disturbance (MLID). This is the first case report of a patient with clinical features of both conditions who was found to have loss of methylation (LOM) of KCNQ1OT1: TSS-DMR (ICR2) in the 11p15 imprinted region associated with BWS and LOM of MEG3: TSS-DMR in the 14q32 imprinted region associated with TS. The report draws attention to the importance of testing for MLID as a cause of atypical clinical presentations of patients with IDs.]]>
Wed, 31 Dec 1969 19:00:00 EST
Molecular mechanisms of transgenerational epigenetic inheritance. Fitz-James MH, Cavalli G
Nat Rev Genet (Jun 2022)

Increasing evidence indicates that non-DNA sequence-based epigenetic information can be inherited across several generations in organisms ranging from yeast to plants to humans. This raises the possibility of heritable 'epimutations' contributing to heritable phenotypic variation and thus to evolution. Recent work has shed light on both the signals that underpin these epimutations, including DNA methylation, histone modifications and non-coding RNAs, and the mechanisms by which they are transmitted across generations at the molecular level. These mechanisms can vary greatly among species and have a more limited effect in mammals than in plants and other animal species. Nevertheless, common principles are emerging, with transmission occurring either via direct replicative mechanisms or indirect reconstruction of the signal in subsequent generations. As these processes become clearer we continue to improve our understanding of the distinctive features and relative contribution of DNA sequence and epigenetic variation to heritable differences in phenotype.]]>
Wed, 31 Dec 1969 19:00:00 EST
Parental and Environmental Control of Seed Dormancy in . Iwasaki M, Penfield S, Lopez-Molina L
Annu Rev Plant Biol (May 2022)

Seed dormancy-the absence of seed germination under favorable germination conditions-is a plant trait that evolved to enhance seedling survival by avoiding germination under unsuitable environmental conditions. In , dormancy levels are influenced by the seed coat composition, while the endosperm is essential to repress seed germination of dormant seeds upon their imbibition. Recent research has shown that the mother plant modulates its progeny seed dormancy in response to seasonal temperature changes by changing specific aspects of seed coat and endosperm development. This process involves genomic imprinting by means of epigenetic marks deposited in the seed progeny and regulators previously known to regulate flowering time. This review discusses and summarizes these discoveries and provides an update on our present understanding of the role of DOG1 and abscisic acid, two key contributors to dormancy.]]>
Wed, 31 Dec 1969 19:00:00 EST
Domain-selective BET inhibition attenuates transcriptional and behavioral responses to cocaine. Singh MB, Babigian CJ, Sartor GC
Neuropharmacology (06 2022)

Epigenetic pharmacotherapies have emerged as a promising treatment option for substance use disorder (SUD) due to their ability to reverse maladaptive transcriptional and behavioral responses to drugs of abuse. In particular, inhibitors of bromodomain and extra terminal domain (BET) reader proteins have been shown to reduce cocaine- and opioid-seeking behaviors in rodents. However, only pan-BET inhibitors, small molecules that bind to both bromodomains (BD1 and BD2) with all BET proteins, have been investigated in animal models of SUD. Given the potential side effects associated with pan-BET inhibitors, safer and more selective strategies are needed to advance BET therapeutics as a potential treatment for SUD. Here, we show that RVX-208, a clinically tested, BD2-selective BET inhibitor, dose-dependently reduced cocaine conditioned place preference in male and female mice, similar to the pan-BET inhibitor JQ1. In other behavioral experiments, RVX-208 treatment did not alter distance traveled, anxiety-like behavior, or novel object recognition memory. At the transcriptional level, RVX-208 attenuated the expression of multiple cocaine-induced genes in the nucleus accumbens in a sex-dependent manner. RVX-208 produced a distinct transcriptional response in stimulated primary neurons compared to JQ1 but had little effect on gene expression in non-stimulated neurons. Together, these data indicate that targeting domain-specific BET mechanisms may be an effective and safer strategy to reduce cocaine-induced neurobehavioral adaptations.]]>
Wed, 31 Dec 1969 19:00:00 EST
Toward Clinical Application of Leukocyte Counts Based on Targeted DNA Methylation Analysis. Sontag S, Bocova L, Hubens WHG, Nüchtern S, Schnitker M, Look T, Schröder KM, Plümäkers B, Tharmapalan V, Wessiepe M, Kraus T, Kramer J, Rink L, Koschmieder S, Wagner W
Clin Chem (May 2022)

Differential leukocyte counts are usually measured based on cellular morphology or surface marker expression. It has recently been shown that leukocyte counts can also be determined by cell-type-specific DNA methylation (DNAm). Such epigenetic leukocyte counting is applicable to small blood volumes and even frozen material, but for clinical translation, the method needs to be further refined and validated.]]>
Wed, 31 Dec 1969 19:00:00 EST
Epigenetic mechanisms affect the curled leaf phenotype in the hypomethylated ddc mutant of Arabidopsis thaliana. Forgione I, Muto A, Woloszynska M, Chiappetta AA, Ferrari M, Van Lijsebettens M, Bitonti MB, Bruno L
Plant Sci (Jun 2022)

The ddc mutant of Arabidopsis thaliana is characterized by pleiotropic phenotypic alterations including a curl-shaped leaf, previously explained by disturbed auxin metabolism and transport. The present study was aimed at further explore the molecular bases underlying the abnormal phenotype of the ddc leaf. We demonstrated that genes specifically related to leaf fate commitment and morphogenesis were misexpressed on developing ddc leaves, such as upregulation of CURLY LEAF (CLF) and downregulation of ASYMMETRIC LEAVES2 (AS2), KNOTTED-like gene from A. thaliana (KNAT6), TEOSINTE-LIKE1 CYCLOIDEA and PROLIFERATING CELL FACTOR 2 (TCP2) and others. The CLF gene, encoding a component of Polycomb repressive complex 2 (PRC2) which adds trimethylation marks at Lys27 of histone H3, was overexpressed in the ddc mutant and concomitantly was correlated with DNA methylation-dependent repression of its negative regulator UCL1. KNAT6, encoding a class 1 KNOX homeotic gene, had increased H3K27me3 trimethylation levels, suggesting it is a target gene of the CLF containing PRC2 complex in the ddc mutant. We postulate that different epigenetic mechanisms modulate expression of genes related to auxin pathways as well as gene targets of Polycomb repressive action, during leaf morphogenesis.]]>
Wed, 31 Dec 1969 19:00:00 EST
Premature Aging of the Airway Epithelium in COPD in People Living with HIV. Kaner RJ
Am J Respir Crit Care Med (May 2022)

Wed, 31 Dec 1969 19:00:00 EST
Lessons from neonatal β-cell epigenomic for diabetes prevention and treatment. Abderrahmani A, Jacovetti C, Regazzi R
Trends Endocrinol Metab (Jun 2022)

Pancreatic β-cell expansion and functional maturation during the birth-to-weaning period plays an essential role in the adaptation of plasma insulin levels to metabolic needs. These events are driven by epigenetic programs triggered by growth factors, hormones, and nutrients. These mechanisms operating in the neonatal period can be at least in part reactivated in adult life to increase the functional β-cell mass and face conditions of increased insulin demand such as obesity or pregnancy. In this review, we will highlight the importance of studying these signaling pathways and epigenetic programs to understand the causes of different forms of diabetes and to permit the design of novel therapeutic strategies to prevent and treat this metabolic disorder affecting hundreds of millions of people worldwide.]]>
Wed, 31 Dec 1969 19:00:00 EST
Aberrant hypomethylation at imprinted differentially methylated regions is involved in biparental placental mesenchymal dysplasia. Aoki S, Higashimoto K, Hidaka H, Ohtsuka Y, Aoki S, Mishima H, Yoshiura KI, Nakabayashi K, Hata K, Yatsuki H, Hara S, Ohba T, Katabuchi H, Soejima H
Clin Epigenetics (May 2022)

Placental mesenchymal dysplasia (PMD) is a morphological abnormality resembling partial hydatidiform moles. It is often associated with androgenetic/biparental mosaicism (ABM) and complicated by Beckwith-Wiedemann syndrome (BWS), an imprinting disorder. These phenomena suggest an association between PMD and aberrant genomic imprinting, particularly of CDKN1C and IGF2. The existence of another type of PMD containing the biparental genome has been reported. However, the frequency and etiology of biparental PMD are not yet fully understood.]]>
Wed, 31 Dec 1969 19:00:00 EST
DNA methylation clocks for dogs and humans. Horvath S, Lu AT, Haghani A, Zoller JA, Li CZ, Lim AR, Brooke RT, Raj K, Serres-Armero A, Dreger DL, Hogan AN, Plassais J, Ostrander EA
Proc Natl Acad Sci U S A (May 2022)

SignificanceEpigenetic estimators of age (known as clocks) allow one to identify interventions that slow or reverse aging. Previous epigenetic clocks only applied to one species at a time. Here, we describe epigenetic clocks that apply to both dogs and humans. These clocks, which measure methylation levels in highly conserved stretches of the DNA, promise to increase the likelihood that interventions that reverse epigenetic age in one species will have the same effect in the other.]]>
Wed, 31 Dec 1969 19:00:00 EST
Developments in high-throughput functional epigenomics: CRISPR-single-cell assay for transposase-accessible chromatin using sequencing screens. E Yan R, P Greenfield J, Dahmane N
Epigenomics (May 2022)

Tweetable abstract CRISPR-scATAC-seq screens pave the way for high-throughput functional epigenomics by linking perturbations to a broad view of epigenetic state and messages hidden within accessible sequences.]]>
Wed, 31 Dec 1969 19:00:00 EST