'; ?> 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 Mon, 28 Nov 2022 15:29:31 EST Mon, 28 Nov 2022 15:29:31 EST jirtle@radonc.duke.edu james001@jirtle.com hyperexpression in two patients with severe growth failure and microdeletions affecting the paternally inherited :TSS-DMR. Hara-Isono K, Yamazawa K, Tanaka S, Nishi E, Fukami M, Kagami M
J Med Genet (Dec 2022)

Two imprinting control centres, :IG-differentialy methylated region (DMR) and :TSS-DMR, reside on chromosome 11p15.5. Paternal deletions involving the :TSS-DMR result in variable phenotypes, namely, normal phenotype, Silver-Russel syndrome (SRS) and fetal demise. However, expression analyses for in these patients are very limited.]]>
Wed, 31 Dec 1969 19:00:00 EST
Novel epigenetic therapeutic strategies and targets in cancer. Babar Q, Saeed A, Tabish TA, Pricl S, Townley H, Thorat N
Biochim Biophys Acta Mol Basis Dis (Dec 2022)

The critical role of dysregulated epigenetic pathways in cancer genesis, development, and therapy has typically been established as a result of scientific and technical innovations in next generation sequencing. RNA interference, histone modification, DNA methylation and chromatin remodelling are epigenetic processes that control gene expression without causing mutations in the DNA. Although epigenetic abnormalities are thought to be a symptom of cell tumorigenesis and malignant events that impact tumor growth and drug resistance, physicians believe that related processes might be a key therapeutic target for cancer treatment and prevention due to the reversible nature of these processes. A plethora of novel strategies for addressing epigenetics in cancer therapy for immuno-oncological complications are currently available - ranging from basic treatment to epigenetic editing. - and they will be the subject of this comprehensive review. In this review, we cover most of the advancements made in the field of targeting epigenetics with special emphasis on microbiology, plasma science, biophysics, pharmacology, molecular biology, phytochemistry, and nanoscience.]]>
Wed, 31 Dec 1969 19:00:00 EST
Computational workflow for integrative analyses of DNA replication timing, epigenomic, and transcriptomic data. Ji F, Van Rechem C, Whetstine JR, Sadreyev RI
STAR Protoc (Dec 2022)

Temporal profiling of DNA replication timing (RT) in combination with chromatin modifications, chromatin accessibility, and gene expression provides new insights into the causal relationships between chromatin and RT during cell cycle. Here, we describe a protocol for in-depth integrative computational analyses of Repli-seq, ATAC-seq, RNA-seq, and ChIP-seq or CUT&RUN data for multiple marks at various time points across cell cycle and changes in their interrelationships upon an experimental perturbation (e.g., knockdown or overexpression of a regulatory protein). For complete details on the use and execution of this protocol, please refer to Van Rechem et al. (2021).]]>
Wed, 31 Dec 1969 19:00:00 EST
Large-scale integration of DNA methylation and gene expression array platforms identifies both and relationships. Lancaster EE, Vladimirov VI, Riley BP, Landry JW, Roberson-Nay R, York TP
Epigenetics (Dec 2022)

Although epigenome-wide association studies (EWAS) have been successful in identifying DNA methylation (DNAm) patterns associated with disease states, any further characterization of etiologic mechanisms underlying disease remains elusive. This knowledge gap does not originate from a lack of DNAm-trait associations, but rather stems from study design issues that affect the interpretability of EWAS results. Despite known limitations in predicting the function of a particular CpG site, most EWAS maintain the broad assumption that altered DNAm results in a concomitant change of transcription at the most proximal gene. This study integrated DNAm and gene expression (GE) measurements in two cohorts, the Adolescent and Young Adult Twin Study (AYATS) and the Pregnancy, Race, Environment, Genes (PREG) study, to improve the understanding of epigenomic regulatory mechanisms. CpG sites associated with GE in were enriched in areas of transcription factor binding and areas of intermediate-to-low CpG density. CpG sites associated with GE were also enriched in areas of known regulatory significance, including enhancer regions. These results highlight issues with restricting DNAm-transcript annotations to small genomic intervals and question the validity of assuming a DNAm-GE pathway. Based on these findings, the interpretation of EWAS results is limited in studies without multi-omic support and further research should identify genomic regions in which GE-associated DNAm is overrepresented. An in-depth characterization of GE-associated CpG sites could improve predictions of the downstream functional impact of altered DNAm and inform best practices for interpreting DNAm-trait associations generated by EWAS.]]>
Wed, 31 Dec 1969 19:00:00 EST
Epigenetic Dysregulation in Autoimmune and Inflammatory Skin Diseases. Gibson F, Hanly A, Grbic N, Grunberg N, Wu M, Collard M, Alani RM
Clin Rev Allergy Immunol (Dec 2022)

Epigenetics is the study of heritable, reversible gene expression patterns that do not originate from alterations in the DNA sequence. Epigenetic modifications influence gene expression patterns and include DNA methylation, histone modifications, and gene regulation via non-coding RNAs. While the study of epigenetics has been most broadly applied to neoplastic diseases, the role of the epigenome in a wide range of disease processes including autoimmune, allergic, and inflammatory processes is increasingly being recognized. Recent advances in the study of the epigenome have led to novel insights into the pathogenesis and potential therapeutic targets of various pathologic entities including inflammatory diseases. In this review, we examine the nature of epigenetic modifications in several well-studied autoimmune, allergic, and/or inflammatory disorders of the skin including systemic lupus erythematosus, vitiligo, systemic sclerosis, alopecia areata, pemphigus, psoriasis, atopic dermatitis, keloidal scarring, and hidradenitis suppurativa with the aim to determine how such epigenetic changes may be targeted for therapeutic benefit.]]>
Wed, 31 Dec 1969 19:00:00 EST
Precise epigenomic editing with a SunTag-based modular epigenetic toolkit. Guhathakurta S, Adams L, Jeong I, Sivakumar A, Cha M, Bernardo Fiadeiro M, Hu HN, Kim YS
Epigenetics (Dec 2022)

Epigenetic regulation is a crucial factor controlling gene expression. Here, we report our CRISPR/dCas9-based modular epigenetic toolkit that enables gene-specific modulation of epigenetic architecture. By modifying the SunTag framework of dCas9 tagged with five GCN4 moieties, each epigenetic writer is bound to scFv and target-specific sgRNA, and this system is able to modify multiple epigenetic marks in a target-specific manner. We successfully demonstrated that this system is efficient in modifying individual histone post-translational modifications. We display its utility as a tool to understand the contributions of specific histone marks on gene expression by screening a large promoter region and identifying differential outcomes with high base-pair resolution. This epigenetic toolkit can be easily altered with a large variety of epigenetic effectors and is a useful tool for researchers to use in understanding gene-specific epigenetic changes and their relation to gene expression.]]>
Wed, 31 Dec 1969 19:00:00 EST
Mapping, clustering, and analysis of research in psychiatric genomics. Yadav S, Chhabra A, Mahesh G
Psychiatr Genet (Dec 2022)

The distribution pattern and knowledge structure of psychiatric genomics were surveyed based on literature dealing with both psychiatry and genomics/genetics. Coword analysis and bibliographic coupling of the records retrieved from Scopus and PubMed for 2016-2020 revealed the subsurface research aspects.]]>
Wed, 31 Dec 1969 19:00:00 EST
Genomic map of candidate human imprint control regions: the imprintome. Jima DD, Skaar DA, Planchart A, Motsinger-Reif A, Cevik SE, Park SS, Cowley M, Wright F, House J, Liu A, Jirtle RL, Hoyo C
Epigenetics (Dec 2022)

Imprinted genes - critical for growth, metabolism, and neuronal function - are expressed from one parental allele. Parent-of-origin-dependent CpG methylation regulates this expression at imprint control regions (ICRs). Since ICRs are established before tissue specification, these methylation marks are similar across cell types. Thus, they are attractive for investigating the developmental origins of adult diseases using accessible tissues, but remain unknown. We determined genome-wide candidate ICRs in humans by performing whole-genome bisulphite sequencing (WGBS) of DNA derived from the three germ layers and from gametes. We identified 1,488 hemi-methylated candidate ICRs, including 19 of 25 previously characterized ICRs (https://humanicr.org/). Gamete methylation approached 0% or 100% in 332 ICRs (178 paternally and 154 maternally methylated), supporting parent-of-origin-specific methylation, and 65% were in well-described CTCF-binding or DNaseI hypersensitive regions. This draft of the human imprintome will allow for the systematic determination of the role of early-acquired imprinting dysregulation in the pathogenesis of human diseases and developmental and behavioural disorders.]]>
Wed, 31 Dec 1969 19:00:00 EST
P16 gene promoter methylation is associated with oncogenesis and progression of gastric carcinomas: A systematic review and meta-analysis. Spagnol LW, Polettini J, Silveira DA, Wegner GRM, Paiva DFF
Crit Rev Oncol Hematol (Dec 2022)

Gastric cancer is the fourth leading cause of neoplastic morbidity worldwide, and its pathogenesis has been related to genetic and epigenetic alterations in cell cycle regulatory genes, such as p16.]]>
Wed, 31 Dec 1969 19:00:00 EST
Extraction and Purification of Single Nuclei from Frozen Human Brain Tissue. Palmer CR, Chun J
Methods Mol Biol (2023)

Resolving the complexity of the human brain at the level of single cells is essential to gaining an understanding of the immense diversity of cell types and functional states in both healthy and diseased brains. To exploit fully the technologies available for such studies, one must extract and isolate pure nuclei from unfixed postmortem tissue while preserving the molecules to be interrogated. Currently, nuclei are necessary substitutes for individual brain cells, since myriad cell types/sub-types constituting the human brain are embedded within the neuropil-a complex milieu of interconnected cells, processes, and synapses-which precludes intact and selective isolation of single brain cells. Here, we describe a protocol for the extraction and purification of intact single nuclei from frozen human brain tissue along with modifications to accommodate numerous downstream analyses, particularly for transcriptomic applications.]]>
Wed, 31 Dec 1969 19:00:00 EST
The role of epigenetics in T-cell lymphoma. Yamagishi M
Int J Hematol (Dec 2022)

Malignant lymphomas are a group of diseases with epigenomic abnormalities fundamental to pathogenesis and pathophysiology. They are characterized by a high frequency of abnormalities related to DNA methylation regulators (DNMT3A, TET2, IDH2, etc.) and histone modifiers (EZH2, HDAC, KMT2D/MLL2, CREBBP, EP300, etc.). These epigenomic abnormalities directly amplify malignant clones. They also originate from a hematopoietic stem cell-derived cell lineage triggered by epigenomic changes. These characteristics are linked to their high affinity for epigenomic therapies. Hematology has led disease epigenetics in the areas of basic research, clinical research, and drug discovery. However, epigenomic regulation is generally recognized as a complex system, and gaps exist between basic and clinical research. To provide an overview of the status and importance of epigenomic abnormalities in malignant lymphoma, this review first summarizes the concept and essential importance of the epigenome, then outlines the current status and future outlook of epigenomic abnormalities in malignant lymphomas.]]>
Wed, 31 Dec 1969 19:00:00 EST
Additive and non-additive epigenetic signatures of natural hybridization between fish species with different mating systems. Berbel-Filho WM, Pacheco G, Lira MG, Garcia de Leaniz C, Lima SMQ, Rodríguez-López CM, Zhou J, Consuegra S
Epigenetics (Dec 2022)

Hybridization is a major source of evolutionary innovation. In plants, epigenetic mechanisms can help to stabilize hybrid genomes and contribute to reproductive isolation, but the relationship between genetic and epigenetic changes in animal hybrids is unclear. We analysed the relationship between genetic background and methylation patterns in natural hybrids of two genetically divergent fish species with different mating systems, (self-fertilizing) and (outcrossing). Co-existing parental species displayed highly distinct genetic (SNPs) and methylation patterns (37,000 differentially methylated cytosines). Hybrids had predominantly intermediate methylation patterns (88.5% of the sites) suggesting additive effects, as expected from hybridization between genetically distant species. The large number of differentially methylated cytosines between hybrids and parental species (n = 5,800) suggests that hybridization may play a role in increasing genetic and epigenetic variation. Although most of the observed epigenetic variation was additive and had a strong genetic component, we also found a small percentage of non-additive, potentially stochastic, methylation differences that might act as an evolutionary bet-hedging strategy and increase fitness under environmental instability.]]>
Wed, 31 Dec 1969 19:00:00 EST
DNA methylation and cell fate in mouse embryos. Clyde D
Nat Rev Genet (Dec 2022)

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Wed, 31 Dec 1969 19:00:00 EST
Prenatal and birth associations of epigenetic gestational age acceleration in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort. Daredia S, Huen K, Van Der Laan L, Collender PA, Nwanaji-Enwerem JC, Harley K, Deardorff J, Eskenazi B, Holland N, Cardenas A
Epigenetics (Dec 2022)

Gestational age (GA) is an important determinant of child health and disease risk. Two epigenetic GA clocks have been developed using DNA methylation (DNAm) patterns in cord blood. We investigate the accuracy of GA clocks and determinants of epigenetic GA acceleration (GAA), a biomarker of biological ageing. We hypothesize that prenatal and birth characteristics are associated with altered GAA, thereby disrupting foetal biological ageing. We examined 372 mother-child pairs from the Center for the Health Assessment of Mothers and Children of Salinas study of primarily Latino farmworkers in California. Chronological GA was robustly correlated with epigenetic GA (DNAm GA) estimated by the Knight ( = 0.48, p < 2.2x10) and Bohlin clocks ( = 0.67, p < 2.2x10) using the Illumina 450K array in cord blood samples collected at birth. GA clock performance was robust, though slightly lower, using DNAm profiles from the Illumina EPIC array in a smaller subsample (Knight: = 0.39, p < 3.5x10; Bohlin: = 0.60, p < 7.7x10). After adjusting for confounders, high maternal serum triglyceride levels (Bohlin: β = -0.01 days per mg/dL, p = 0.03), high maternal serum lipid levels (Bohlin: β = -4.31x10 days per mg/dL, p = 0.04), preterm delivery (Bohlin: β = -4.03 days, p = 9.64x10), greater maternal parity (Knight: β = -4.07 days, p = 0.01; Bohlin: β = -2.43 days, p = 0.01), and male infant sex (Knight: β = -3.15 days, p = 3.10x10) were associated with decreased GAA.Prenatal and birth characteristics affect GAA in newborns. Understanding factors that accelerate or delay biological ageing at birth may identify early-life targets for disease prevention and improve ageing across the life-course. Future research should test the impact of altered GAA on the long-term burden of age-related diseases.]]>
Wed, 31 Dec 1969 19:00:00 EST
Epigenomic and somatic mutations of pituitary tumors with clinical and pathological correlations in 111 patients. Guaraldi F, Morandi L, Zoli M, Mazzatenta D, Righi A, Evangelisti S, Ambrosi F, Tonon C, Giannini C, Lloyd RV, Asioli S
Clin Endocrinol (Oxf) (Dec 2022)

To profile clinically non-aggressive and aggressive pituitary adenomas (PAs)/pituitary neuroendocrine tumours (PitNETs) and pituitary carcinomas for somatic mutations and epigenetic alterations of genes involved in cell proliferation/differentiation, microRNAs (miRNA)/long noncoding RNA (LncRNA)-post-transcriptional regulators and therapy targets.]]>
Wed, 31 Dec 1969 19:00:00 EST
Genome-wide methylation analysis of early-onset schizophrenia. Srivastava A, Chaudhary Z, Qian J, Al Chalabi N, Burhan AM, Fischer CE, Gerretsen P, Kolla NJ, Graff A, Remington G, De Luca V
Psychiatr Genet (Dec 2022)

Schizophrenia (SCZ) is a debilitating disease with a complex genetic cause in which age at onset may reflect genetic vulnerability. Though there has been some association between genetic polymorphisms and age of onset, there has been little exploration of the role of epigenetic processes. We sought to explore the influence of DNA methylation, a key epigenetic mechanism, and its association with the age of onset of illness.]]>
Wed, 31 Dec 1969 19:00:00 EST
Sex-biased expression of the TLR7 gene in severe COVID-19 patients: Insights from transcriptomics and epigenomics. Gómez-Carballa A, Pardo-Seco J, Pischedda S, Rivero-Calle I, Butler-Laporte G, Richards JB, Viz-Lasheras S, Martinón-Torres F, Salas A,  
Environ Res (Dec 2022)

There is abundant epidemiological data indicating that the incidence of severe cases of coronavirus disease (COVID-19) is significantly higher in males than females worldwide. Moreover, genetic variation at the X-chromosome linked TLR7 gene has been associated with COVID-19 severity. It has been suggested that the sex-biased incidence of COVID-19 might be related to the fact that TLR7 escapes X-chromosome inactivation during early embryogenesis in females, thus encoding a doble dose of its gene product compared to males. We analyzed TLR7 expression in two acute phase cohorts of COVID-19 patients that used two different technological platforms, one of them in a multi-tissue context including saliva, nasal, and blood samples, and a third cohort that included different post-infection timepoints of long-COVID-19 patients. We additionally explored methylation patterns of TLR7 using epigenomic data from an independent cohort of COVID-19 patients stratified by severity and sex. In line with genome-wide association studies, we provide supportive evidence indicating that TLR7 has altered CpG methylation patterns and it is consistently downregulated in males compared to females in the most severe cases of COVID-19.]]>
Wed, 31 Dec 1969 19:00:00 EST
Measuring biological age using omics data. Rutledge J, Oh H, Wyss-Coray T
Nat Rev Genet (Dec 2022)

Age is the key risk factor for diseases and disabilities of the elderly. Efforts to tackle age-related diseases and increase healthspan have suggested targeting the ageing process itself to 'rejuvenate' physiological functioning. However, achieving this aim requires measures of biological age and rates of ageing at the molecular level. Spurred by recent advances in high-throughput omics technologies, a new generation of tools to measure biological ageing now enables the quantitative characterization of ageing at molecular resolution. Epigenomic, transcriptomic, proteomic and metabolomic data can be harnessed with machine learning to build 'ageing clocks' with demonstrated capacity to identify new biomarkers of biological ageing.]]>
Wed, 31 Dec 1969 19:00:00 EST
Prenatal lead (Pb) exposure is associated with differential placental DNA methylation and hydroxymethylation in a human population. Tung PW, Kennedy EM, Burt A, Hermetz K, Karagas M, Marsit CJ
Epigenetics (Dec 2022)

Prenatal lead (Pb) exposure is associated with adverse developmental outcomes and to epigenetic alterations such as DNA methylation and hydroxymethylation in animal models and in newborn blood. Given the importance of the placenta in foetal development, we sought to examine how prenatal Pb exposure was associated with differential placental DNA methylation and hydroxymethylation and to identify affected biological pathways linked to developmental outcomes. Maternal (n = 167) and infant (n = 172) toenail and placenta (n = 115) samples for prenatal Pb exposure were obtained from participants in a US birth cohort, and methylation and hydroxymethylation data were quantified using the Illumina Infinium MethylationEPIC BeadChip. An epigenome-wide association study was applied to identify differential methylation and hydroxymethylation associated with Pb exposure. Biological functions of the Pb-associated genes were determined by overrepresentation analysis through ConsensusPathDB. Prenatal Pb quantified from maternal toenail, infant toenail, and placenta was associated with 480, 27, and 2 differentially methylated sites (q < 0.05), respectively, with both increases and decreases associated with exposure. Alternatively, we identified 2, 1, and 14 differentially hydroxymethylated site(s) associated with maternal toenail, infant toenail, and placental Pb, respectively, with most showing increases in hydroxymethylation with exposure. Significantly overrepresented pathways amongst genes associated with differential methylation and hydroxymethylation (q < 0.10) included mechanisms pertaining to nervous system and organ development, calcium transport and regulation, and signalling activities. Our results suggest that both methylation and hydroxymethylation in the placenta can be variable based on Pb exposure and that the pathways impacted could affect placental function.]]>
Wed, 31 Dec 1969 19:00:00 EST
How paediatric drug development and use could benefit from OMICs: A c4c expert group white paper. Neumann E, Schreeck F, Herberg J, Jacqz Aigrain E, Maitland-van der Zee AH, Pérez-Martínez A, Hawcutt DB, Schaeffeler E, Rane A, de Wildt SN, Schwab M
Br J Clin Pharmacol (Dec 2022)

The safety and efficacy of pharmacotherapy in children, particularly preterms, neonates and infants, is limited by a paucity of good-quality data from prospective clinical drug trials. A specific challenge is the establishment of valid biomarkers. OMICs technologies may support these efforts by complementary information about targeted and nontargeted molecules through systematic characterization and quantitation of biological samples. OMICs technologies comprise at least genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiomics in addition to the patient's phenotype. OMICs technologies are in part hypothesis-generating, allowing an in depth understanding of disease pathophysiology and pharmacological mechanisms. Application of OMICs technologies in paediatrics faces major challenges before routine adoption. First, developmental processes need to be considered, including a subdivision into specific age groups as developmental changes clearly impact OMICs data. Second, compared to the adult population, the number of patients is limited as are the type and amount of necessary biomaterial, especially in neonates and preterms. Thus, advanced trial designs and biostatistical methods, noninvasive biomarkers, innovative biobanking concepts including data and samples from healthy children, as well as analytical approaches (eg liquid biopsies) should be addressed to overcome these obstacles. The ultimate goal is to link OMICs technologies with innovative analysis tools, such as artificial intelligence at an early stage. The use of OMICs data based on a feasible approach will contribute to the identification complex phenotypes and subpopulations of patients to improve the development of medicines for children with potential economic advantages.]]>
Wed, 31 Dec 1969 19:00:00 EST