'; ?> 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 Thu, 01 Dec 2022 16:08:34 EST Thu, 01 Dec 2022 16:08:34 EST jirtle@radonc.duke.edu james001@jirtle.com 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 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 Life-course socioeconomic factors are associated with markers of epigenetic aging in a population-based study. Petrovic D, Carmeli C, Sandoval JL, Bodinier B, Chadeau-Hyam M, Schrempft S, Ehret G, Dhayat NA, Ponte B, Pruijm M, Vineis P, Gonseth-Nusslé S, Guessous I, McCrory C, Bochud M, Stringhini S
Psychoneuroendocrinology (Jan 2023)

Adverse socioeconomic circumstances negatively affect the functioning of biological systems, but the underlying mechanisms remain only partially understood. Here, we explore the associations between life-course socioeconomic factors and four markers of epigenetic aging in a population-based setting. We included 684 participants (52 % women, mean age 52.6 ± 15.5 years) from a population and family-based Swiss study. We used nine life-course socioeconomic indicators as the main exposure variables, and four blood-derived, second generation markers of epigenetic aging as the outcome variables (Levine's DNAmPhenoAge, DunedinPoAm38, GrimAge epigenetic age acceleration (EAA), and the mortality risk score (MS)). First, we investigated the associations between socioeconomic indicators and markers of epigenetic aging via mixed-effect linear regression models, adjusting for age, sex, participant's recruitment center, familial structure (random-effect covariate), seasonality of blood sampling, and technical covariates. Second, we implemented counterfactual mediation analysis to investigate life-course and intermediate mechanisms underlying the socioeconomic gradient in epigenetic aging. Effect-size estimates were assessed using regression coefficients and counterfactual mediation parameters, along with their respective 95 % confidence intervals. Individuals reporting a low father's occupation, adverse financial conditions in childhood, a low income, having financial difficulties, or experiencing unfavorable socioeconomic trajectories were epigenetically older and had a higher mortality risk score than their more advantaged counterparts. Specifically, this corresponded to an average increase of 1.1-1.5 years for Levine's epigenetic age (β and 95 %CI range, β (minimum and maximum): 1.1-1.5 95 %CI[0.0-0.2; 2.3-3.0]), 1.1-1.5 additional years for GrimAge (β: 1.1-1.5 95 %CI[0.2-0.6; 1.9-3.0]), a 1-3 % higher DunedinPoAm38 age acceleration (β: 0.01-0.03 95 %CI[0.00; 0.03-0.04]), and a 10-50 % higher MS score (β: 0.1-0.4 95 %CI[0.0-0.2; 0.3-0.4]) for the aforementioned socioeconomic indicators. By exploring the life-course mechanisms underlying the socioeconomic gradient in epigenetic aging, we found that both childhood and adulthood socioeconomic factors contributed to epigenetic aging, and that detrimental lifestyle factors mediated the relation between socioeconomic circumstances in adulthood and EAA (31-89 % mediated proportion). This study provides emerging evidence for an association between disadvantaged life-course socioeconomic circumstances and detrimental epigenetic aging patterns, supporting the "sensitive-period" life-course model. Counterfactual mediation analyses further indicated that the effect of socioeconomic factors in adulthood operates through detrimental lifestyle factors, whereas associations involving early-life socioeconomic factors were less clear.]]> 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 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 DNA methylation and cell fate in mouse embryos. Clyde D
Nat Rev Genet (Dec 2022)

]]> 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 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 Early microbial exposure shapes adult immunity by altering CD8+ T cell development. Tabilas C, Iu DS, Daly CWP, Yee Mon KJ, Reynaldi A, Wesnak SP, Grenier JK, Davenport MP, Smith NL, Grimson A, Rudd BD
Proc Natl Acad Sci U S A (Dec 2022)

Microbial exposure during development can elicit long-lasting effects on the health of an individual. However, how microbial exposure in early life leads to permanent changes in the immune system is unknown. Here, we show that the microbial environment alters the set point for immune susceptibility by altering the developmental architecture of the CD8+ T cell compartment. In particular, early microbial exposure results in the preferential expansion of highly responsive fetal-derived CD8+ T cells that persist into adulthood and provide the host with enhanced immune protection against intracellular pathogens. Interestingly, microbial education of fetal-derived CD8+ T cells occurs during thymic development rather than in the periphery and involves the acquisition of a more effector-like epigenetic program. Collectively, our results provide a conceptual framework for understanding how microbial colonization in early life leads to lifelong changes in the immune system.]]> Wed, 31 Dec 1969 19:00:00 EST Rapid Single-Pot Assembly of Modular Chromatin Proteins for Epigenetic Engineering. Haynes KA, Priode JH
Methods Mol Biol (2023)

Chromatin is the nucleoprotein complex that organizes genomic DNA in the nuclei of eukaryotic cells. Chromatin-modifying enzymes and chromatin-binding regulators generate chromatin states that affect DNA compaction, repair, gene expression, and ultimately cell phenotype. Many natural chromatin mediators contain subdomains that can be isolated and recombined to build synthetic regulators and probes. Engineered chromatin proteins make up a growing collection of new tools for cell engineering and can help deepen our understanding of the mechanism by which chromatin features, such as modifications of histones and DNA, contribute to the epigenetic states that govern DNA-templated processes. To support efficient exploration of the large combinatorial design space of synthetic chromatin proteins, we have developed a Golden Gate assembly method for one-step construction of protein-encoding recombinant DNA. A set of standard 2-amino acid linkers allows facile assembly of any combination of up to four protein modules, obviating the need to design different compatible overhangs to ligate different modules. Beginning with the identification of protein modules of interest, a synthetic chromatin protein can be built and expressed in vitro or in cells in under 2 weeks.]]> Wed, 31 Dec 1969 19:00:00 EST Stable methylation loci are associated with systolic blood pressure in a Croatian island population. Sprague AC, Niu L, Jandarov R, Zhang X, Zhang G, Chen A, Å arac J, Čoklo M, Missoni S, Rudan P, Langevin SM, Deka R
Epigenomics (Dec 2022)

The objective was to identify stable and dynamic DNA methylation loci associated with cardiometabolic traits among an adult population from the Croatian island of Hvar. An epigenome-wide association study was conducted using peripheral blood longitudinally collected at two time points 10 years apart via Infinium MethylationEPIC beadarray (n = 112). Stable and dynamic loci were identified using linear mixed models. Associations between cardiometabolic traits and loci were assessed using linear models. 22 CpG loci were significantly associated with systolic blood pressure. Twenty were stable and two were dynamic. Multiple genes may be involved in the determination of systolic blood pressure level via stable epigenetic programming, potentially established earlier in life.]]> 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 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 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 Machine learning applications for transcription level and phenotype predictions. Chantaraamporn J, Phumikhet P, Nguantad S, Techo T, Charoensawan V
IUBMB Life (Dec 2022)

Predicting phenotypes and complex traits from genomic variations has always been a big challenge in molecular biology, at least in part because the task is often complicated by the influences of external stimuli and the environment on regulation of gene expression. With today's abundance of omic data and advances in high-throughput computing and machine learning (ML), we now have an unprecedented opportunity to uncover the missing links and molecular mechanisms that control gene expression and phenotypes. To empower molecular biologists and researchers in related fields to start using ML for in-depth analyses of their large-scale data, here we provide a summary of fundamental concepts of machine learning, and describe a wide range of research questions and scenarios in molecular biology where ML has been implemented. Due to the abundance of data, reproducibility, and genome-wide coverage, we focus on transcriptomics, and two ML tasks involving it: (a) predicting of transcriptomic profiles or transcription levels from genomic variations in DNA, and (b) predicting phenotypes of interest from transcriptomic profiles or transcription levels. Similar approaches can also be applied to more complex data such as those in multi-omic studies. We envisage that the concepts and examples described here will raise awareness and promote the application of ML among molecular biologists, and eventually help improve a framework for systematic design and predictions of gene expression and phenotypes for synthetic biology applications.]]> 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 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 LncRNAs in neuropsychiatric disorders and computational insights for their prediction. Baruah C, Nath P, Barah P
Mol Biol Rep (Dec 2022)

Long non-coding RNAs (lncRNAs) are 200 nucleotide extended transcripts that do not encode proteins or possess limited coding ability. LncRNAs epigenetically control several biological functions such as gene regulation, transcription, mRNA splicing, protein interaction, and genomic imprinting. Over the years, drastic progress in understanding the role of lncRNAs in diverse biological processes has been made. LncRNAs are reported to show tissue-specific expression patterns suggesting their potential as novel candidate biomarkers for diseases. Among all other non-coding RNAs, lncRNAs are highly expressed within the brain-enriched or brain-specific regions of the neural tissues. They are abundantly expressed in the neocortex and pre-mature frontal regions of the brain. LncRNAs are co-expressed with the protein-coding genes and have a significant role in the evolution of functions of the brain. Any deregulation in the lncRNAs contributes to disruptions in normal brain functions resulting in multiple neurological disorders. Neuropsychiatric disorders such as schizophrenia, bipolar disease, autism spectrum disorders, and anxiety are associated with the abnormal expression and regulation of lncRNAs. This review aims to highlight the understanding of lncRNAs concerning normal brain functions and their deregulation associated with neuropsychiatric disorders. We have also provided a survey on the available computational tools for the prediction of lncRNAs, their protein coding potentials, and sub-cellular locations, along with a section on existing online databases with known lncRNAs, and their interactions with other molecules.]]> Wed, 31 Dec 1969 19:00:00 EST Changes in epigenetic information during the occurrence and development of gastric cancer. Li N, Meng G, Yang C, Li H, Liu L, Wu Y, Liu B
Int J Biochem Cell Biol (Dec 2022)

Gastric cancer is one of the most common malignant tumors of the digestive tract, with a high degree of malignancy and poor prognosis. With advancements in disease research, the role of epigenetic changes in its pathogenesis has become a research focus. The known epigenetic changes mainly include DNA methylation, histone modification, and regulation of chromatin structure. This article details the effects of these changes that would result in gastric cancer. Using next-generation sequencing methods and bioinformatics analysis, we can determine the epigenetic changes in abnormal tissues of the digestive tract that facilitate the early diagnosis and treatment of gastric cancer patients. In this article, we summarize how epigenetic changes determine gastric cancer and the new technologies used in research on cancer to benefit gastric cancer patients.]]> 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