'; ?> 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 Sat, 28 Jan 2023 01:16:24 EST Sat, 28 Jan 2023 01:16:24 EST jirtle@radonc.duke.edu james001@jirtle.com Three-dimensional chromatin architecture datasets for aging and Alzheimer's disease. Meng G, Xu H, Lu D, Li S, Zhao Z, Li H, Zhang W
Sci Data (Jan 2023)

Recently, increasing studies are indicating a close association between dysregulated enhancers and neurodegenerative diseases, such as Alzheimer's disease (AD). However, their contributions were poorly defined for lacking direct links to disease genes. To bridge this gap, we presented the Hi-C datasets of 4 AD patients, 4 dementia-free aged and 3 young subjects, including 30 billion reads. As applications, we utilized them to link the AD risk SNPs and dysregulated epigenetic marks to the target genes. Combining with epigenetic data, we observed more detailed interactions among regulatory regions and found that many known AD risk genes were under long-distance promoter-enhancer interactions. For future AD and aging studies, our datasets provide a reference landscape to better interpret findings of association and epigenetic studies for AD and aging process.]]>
Wed, 31 Dec 1969 19:00:00 EST
A 132 bp deletion affecting the gene associated with Silver-Russell syndrome clinical phenotype. Gaudet MV, Allain EP, Gallant LM, Arts HH, Ben Amor M
J Med Genet (Feb 2023)

Imprinting centre 2 (IC2) in the chromosomal region 11p15.5 regulates the monoallelic expression of imprinted genes by differential methylation of paternal and maternal chromosomes. Copy number variants in IC2 are associated with Beckwith-Wiedemann syndrome and Silver-Russell syndrome (SRS). Clinical outcome of IC2 deletions seems to depend on the parental origin of the chromosome, deletion size and inclusion or exclusion of enhancer and promoter regions.]]>
Wed, 31 Dec 1969 19:00:00 EST
Fifty years of basic and clinical renal stone research: have we achieved major breakthroughs? A debate. Rodgers A, Trinchieri A
Curr Opin Nephrol Hypertens (Mar 2023)

After 50 years of basic and clinical renal stone research, it is appropriate to evaluate whether breakthroughs have been achieved and if so, how they may be harnessed to combat stone disease therapeutically and prophylactically.]]>
Wed, 31 Dec 1969 19:00:00 EST
Executive functioning in adolescents and adults with Silver-Russell syndrome. Burgevin M, Lacroix A, Ollivier F, Bourdet K, Coutant R, Donadille B, Faivre L, Manouvrier-Hanu S, Petit F, Thauvin-Robinet C, Toutain A, Netchine I, Odent S
PLoS One (2023)

Silver-Russell syndrome (SRS) is a rare imprinting disorder characterized by prenatal and postnatal growth retardation. The two principal causes of SRS are loss of methylation on chromosome 11p15 (11p15 LOM) and maternal uniparental disomy of chromosome 7 (UPD(7)mat). Knowledge of the neuropsychological profile of SRS remains sparse and incomplete even if several difficulties related to attention and learning have been reported both in the literature and by patients with SRS. These difficulties could be the result of troubles in different cognitive domains, but also of executive dysfunction. Nevertheless, executive functioning has never been investigated, even though executive functions play an essential role in psychological development, and are extensively involved in daily life. The present study explored the executive functioning of individuals with SRS due to UPD(7)mat or 11p15 LOM. A battery of executive tasks assessing cognitive flexibility, inhibitory control, and working memory, together with a task assessing sustained attention, was administered to 19 individuals with SRS (13-39 years) and 19 healthy controls. The Behavior Rating Inventory of Executive Function was also completed by the participants' families. The results showed that participants with SRS had similar performance (z-scores) to our controls, in a context of normal intellectual efficiency. Group comparisons with Bayesian statistics showed a single difference between the 11p15 LOM and control groups: the completion time for part A of the Trail Making Test appeared to be longer in the 11p15 LOM group than in the control group. However, at the clinical level, several participants with SRS had clinically significant scores on various measures of EFs. Thus, the cognitive phenotype of SRS did not appear to be characterized by executive dysfunction, but individuals with SRS could be at high risk of developing executive dysfunction or attention-deficit/hyperactivity disorder. These results provide new insights into the neuropsychological profile of individuals with SRS.]]>
Wed, 31 Dec 1969 19:00:00 EST
Novel RNA N6-methyladenosine regulator related signature for predicting clinical and immunological characteristics in breast cancer. Zhang J, Liu G, Dai Z, Xie F, Zheng R, Yuan B, Guo L
Gene (Feb 2023)

Epigenetic mechanismshave been reported to involve in shaping tumor immune microenvironment (TME). However, the role of RNA N6-methyladenosine (m6A) modification in breast cancerhas not been fully explored.]]>
Wed, 31 Dec 1969 19:00:00 EST
Mechanistic insights into dietary (poly)phenols and vascular dysfunction-related diseases using multi-omics and integrative approaches: Machine learning as a next challenge in nutrition research. Milenkovic D, Ruskovska T
Mol Aspects Med (Feb 2023)

Dietary (poly)phenols have been extensively studied for their vasculoprotective effects and consequently their role in preventing or delaying onsets of cardiovascular and metabolic diseases. Even though early studies have ascribed the vasculoprotective properties of (poly)phenols primarily on their putative free radical scavenging properties, recent data indicate that in biological systems, (poly)phenols act primarily through genomic and epigenomic mechanisms. The molecular mechanisms underlying their health properties are still not well identified, mainly due to the use of physiologically non-relevant conditions (native molecules or extracts at high concentrations, rather than circulating metabolites), but also due to the use of targeted genomic approaches aiming to evaluate the effect only on few specific genes, thus preventing to decipher detailed molecular mechanisms involved. The use of state-of-the-art untargeted analytical methods represents a significant breakthrough in nutrigenomics, as these methods enable detailed insights into the effects at each specific omics level. Moreover, the implementation of multi-omics approaches allows integration of different levels of regulation of cellular functions, to obtain a comprehensive picture of the molecular mechanisms of action of (poly)phenols. In combination with bioinformatics and the methods of machine learning, multi-omics has potential to make a huge contribution to the nutrition science. The aim of this review is to provide an overview of the use of the omics, multi-omics, and integrative approaches in studying the vasculoprotective properties of dietary (poly)phenols and address the potentials for use of the machine learning in nutrigenomics.]]>
Wed, 31 Dec 1969 19:00:00 EST
Diagnosis of Prader-Willi syndrome and Angelman syndrome by targeted nanopore long-read sequencing. Yamada M, Okuno H, Okamoto N, Suzuki H, Miya F, Takenouchi T, Kosaki K
Eur J Med Genet (Feb 2023)

The CpG island flanking the promoter region of SNRPN on chromosome 15q11.2 contains CpG sites that are completely methylated in the maternally derived allele and unmethylated in the paternally derived allele. Both unmethylated and methylated alleles are observed in normal individuals. Only the methylated allele is observed in patients with Prader-Willi syndrome, whereas only the unmethylated allele is observed in those with Angelman syndrome. Hence, detection of aberrant methylation at the differentially methylated region is fundamental to the molecular diagnosis of Prader-Willi syndrome and Angelman syndromes. Traditionally, bisulfite treatment and methylation-sensitive restriction enzyme treatment or methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) have been used. We here developed a long-read sequencing assay that can distinguish methylated and unmethylated CpG sites at 15q11.2 by the difference in current intensity generated from nanopore reads. We successfully diagnosed 4 Prader-Willi syndrome patients and 3 Angelman syndrome patients by targeting differentially methylated regions. Concurrent copy number analysis, homozygosity analysis, and structural variant analysis also allowed us to precisely delineate the underlying pathogenic mechanisms, including gross deletion, uniparental heterodisomy, uniparental isodisomy, or imprinting defect. Furthermore, we showed allele-specific methylation in imprinting-related differentially methylated regions on chromosomes 6, 7, 11, 14, and 20 in a normal individual together with 4 Prader-Willi patients and 3 Angelman syndrome patients. Hence, presently reported method is likely to be applicable to the diagnosis of imprinting disorders other than Prader-Willi syndrome and Angelman syndrome as well.]]>
Wed, 31 Dec 1969 19:00:00 EST
Gos: a declarative library for interactive genomics visualization in Python. Manz T, L'Yi S, Gehlenborg N
Bioinformatics (Jan 2023)

Gos is a declarative Python library designed to create interactive multiscale visualizations of genomics and epigenomics data. It provides a consistent and simple interface to the flexible Gosling visualization grammar. Gos hides technical complexities involved with configuring web-based genome browsers and integrates seamlessly within computational notebooks environments to enable new interactive analysis workflows.]]>
Wed, 31 Dec 1969 19:00:00 EST
Comprehensive 100-bp resolution genome-wide epigenomic profiling data for the hg38 human reference genome. Li RY, Huang Y, Zhao Z, Qin ZS
Data Brief (Feb 2023)

This manuscript presents a comprehensive collection of diverse epigenomic profiling data for the human genome in 100-bp resolution with full genome-wide coverage. The datasets are processed from raw read count data collected from five types of sequencing-based assays collected by the Encyclopedia of DNA Elements consortium (ENCODE, http://www.encodeproject.org). Data from high-throughput sequencing assays were processed and crystallized into a total of 6,305 genome-wide profiles. To ensure the quality of the features, we filtered out assays with low read depth, inconsistent read counts, and poor data quality. The types of sequencing-based experiment assays include DNase-seq, histone and TF ChIP-seq, ATAC-seq, and Poly(A) RNA-seq. Merging of processed data was done by averaging read counts across technical replicates to obtain signals in about 30 million predefined 100-bp bins that tile the entire genome. We provide an example of fetching read counts using disease-related risk variants from the GWAS Catalog. Additionally, we have created a tabix index enabling fast user retrieval of read counts given coordinates in the human genome. The data processing pipeline is replicable for users' own purposes and for other experimental assays. The processed data can be found on Zenodo at https://zenodo.org/record/7015783. These data can be used as features for statistical and machine learning models to predict or infer a wide range of variables of biological interest. They can also be applied to generate novel insights into gene expression, chromatin accessibility, and epigenetic modifications across the human genome. Finally, the processing pipeline can be easily applied to data from any other genome-wide profiling assays, expanding the amount of available data.]]>
Wed, 31 Dec 1969 19:00:00 EST
Pesticide exposure affects DNA methylation patterns in natural populations of a mayfly. Gouin N, Notte AM, Kolok AS, Bertin A
Sci Total Environ (Mar 2023)

Chemical pollutants derived from agricultural activities represent a major threat to freshwater biota. Despite growing evidence involving epigenetic processes, such as DNA methylation, in response to pesticide contamination in agroecosystems, research on wild populations of non-model species remains scarce, particularly for endemic freshwater arthropods. Using the MethylRAD method, this study investigates whether exposure to pesticide contamination in natural populations of the endemic mayfly A. torrens produces genome wide changes in levels of DNA methylation. From a total of 1,377,147 MethylRAD markers produced from 285 specimens collected at 30 different study sites along the Limarí watershed of north-central Chile, six showed significant differential methylation between populations exposed and unexposed to pesticides. In all cases the effect of pesticides was positive, independent and stronger than the effects detected for other spatial and environmental factors. Only one candidate marker appeared correlated significantly with additional variables, nitrate and calcium levels, which also reflects the impact of agrichemicals and could additionally suggest, to a lower extent, antagonistic effects of mineral salts concentration for this specific marker. These results suggest that the effect of pesticide exposure on methylation levels is apparent at these six MethylRAD markers in A. torrens populations. Such data is challenging to obtain in natural populations and is, for the most part, lacking in ecotoxicological studies. Our study shows that DNA methylation processes are involved in the response to pesticide contamination in populations of the mayfly A. torrens in their natural habitat, and provides new evidence regarding the impact of pesticide contamination and agricultural activities on the endemic fauna of lotic ecosystems.]]>
Wed, 31 Dec 1969 19:00:00 EST
Chemistry revolutionizes genetics and epigenetics. Yoshida M, Park SB
Curr Opin Chem Biol (Feb 2023)

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Wed, 31 Dec 1969 19:00:00 EST
Maternal versus paternal inheritance of a 132 bp 11p15.5 microdeletion affecting and associated phenotypes. Stoltze UK, Hansen TVO, Brok JS, Grønskov K, Tumer AZ, Ahlborn LB, Schmiegelow K, Wadt KAW
J Med Genet (Feb 2023)

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Wed, 31 Dec 1969 19:00:00 EST
Familial Beckwith-Wiedemann syndrome in a multigenerational family: Forty years of careful phenotyping. Best LG, Duffy KA, George AM, Ganguly A, Kalish JM
Am J Med Genet A (Feb 2023)

Beckwith-Wiedemann Spectrum (BWSp) is an overgrowth and cancer predisposition disorder characterized by a wide spectrum of phenotypic manifestations including macroglossia, abdominal wall defects, neonatal hypoglycemia, and predisposition to embryonal tumors. In 1981, Best and Hoekstra reported four patients with BWSp in a single family which suggested autosomal dominant inheritance, but standard clinical testing for BWSp was not available during this time. Meticulous phenotyping of this family has occurred over the past 40 years of follow-up with additional family members being identified and samples collected for genetic testing. Genetic testing revealed a pathogenic mutation in CDKN1C, consistent with the most common cause of familial BWSp. CDKN1C mutations account for just 5% of sporadic cases of BWSp. Here, we report the variable presentation of BWSp across the individuals affected by the CDKN1C mutation and other extended family members spanning multiple generations, all examined by the same physician. Additional phenotypes thought to be atypical in patients with BWSp were reported which included cardiac abnormalities. The incidence of tumors was documented in extended family members and included rhabdomyosarcoma, astrocytoma, and thyroid carcinoma, which have previously been reported in patients with BWSp. These observations suggest that in addition to the inheritance of the CDKN1C variant, there are modifying factors in this family driving the phenotypic spectrum observed. Alternative theories are suggested to explain the etiology of clinical variability including diffused mosaicism, anticipation, and the presence of additional variants tracking in the family. This study highlights the necessity of long-term follow-up in patients with BWSp and consideration of individual familial characteristics in the context of phenotype and/or (epi)genotype associations.]]>
Wed, 31 Dec 1969 19:00:00 EST
Genomic and epigenomic variation in Psidium species and their outcome under the yield and composition of essential oils. Silva MA, Soares FAF, Clarindo WR, Mendes LA, Alves LB, Ferreira A, da Silva Ferreira MF
Sci Rep (Jan 2023)

Diploid and polyploid species derived from the euploid series x = 11 occur in the genus Psidium, as well as intraspecific cytotypes. Euploidy in the genus can alter the gene copy number, resulting in several "omics" variations. We revisited the euploidy, reported genomic (nuclear 2C value, GC%, and copy number of secondary metabolism genes) and epigenomic (5-mC%) differences in Psidium, and related them to essential oil yield and composition. Mean 2C values ranged from 0.90 pg (P. guajava) to 7.40 pg (P. gaudichaudianum). 2C value is intraspecifically varied in P. cattleyanum and P. gaudichaudianum, evidencing cytotypes that can be formed from euploid (non-reduced) and/or aneuploid reproductive cells. GC% ranged from 34.33% (P. guineense) to 48.95% (P. myrtoides), and intraspecific variations occurred even for species without 2C value intraspecific variation. Essential oil yield increased in relation to 2C value and to GC%. We showed that P. guajava (diploid) possesses two and P. guineense (tetraploid) four copies of the one specific TPS gene, as well as eight and sixteen copies respectively of the conserved regions that occur in eight TPS genes. We provide a wide "omics'' characterization of Psidium and show the outcome of the genome and epigenome variation in secondary metabolism.]]>
Wed, 31 Dec 1969 19:00:00 EST
Coupling epigenetics and RNA polyadenylation: missing links. Lin J, Li QQ
Trends Plant Sci (Feb 2023)

Precise regulation of gene expression is crucial for plant survival. As a cotranscriptional regulatory mechanism, pre-mRNA polyadenylation is essential for fine-tuning gene expression. Polyadenylation can be alternatively projected at various sites of a transcript, which contributes to transcriptome diversity. Epigenetic modification is another mechanism of transcriptional control. Recent studies have uncovered crosstalk between cotranscriptional polyadenylation processes and both epigenomic and epitranscriptomic markers. Genetic analyses have demonstrated that DNA methylation, histone modifications, and epitranscriptomic modification are involved in regulating polyadenylation in plants. Here we summarize current understanding of the links between epigenetics and polyadenylation and their novel biological efficacy for plant development and environmental responses. Unresolved issues and future directions are discussed to shed light on the field.]]>
Wed, 31 Dec 1969 19:00:00 EST
Common Variable Immunodeficiency: More Pathways than Roads to Rome. Peng XP, Caballero-Oteyza A, Grimbacher B
Annu Rev Pathol (Jan 2023)

Fifty years have elapsed since the term common variable immunodeficiency (CVID) was introduced to accommodate the many and varied antibody deficiencies being identified in patients with suspected inborn errors of immunity (IEIs). Since then, how the term is understood and applied for diagnosis and management has undergone many revisions, though controversy persists on how exactly to define and classify CVID. Many monogenic disorders have been added under its aegis, while investigations into polygenic, epigenetic, and somatic contributions to CVID susceptibility have gained momentum. Expansion of the overall IEI landscape has increasingly revealed genotypic and phenotypic overlap between CVID and various other immunological conditions, while increasingly routine genotyping of CVID patients continues to identify an incredible diversity of pathophysiological mechanisms affecting even single genes. Though many questions remain to be answered, the lessons we have already learned from CVID biology have greatly informed our understanding of adaptive, but also innate, immunity.]]>
Wed, 31 Dec 1969 19:00:00 EST
Integrative epigenomics in chronic lymphocytic leukaemia: Biological insights and clinical applications. Kulis M, Martin-Subero JI
Br J Haematol (Feb 2023)

Chronic lymphocytic leukaemia (CLL) is not only characterised by driver genetic alterations but by extensive epigenetic changes. Over the last decade, epigenomic studies have described the DNA methylome, chromatin accessibility, histone modifications and the three-dimensional (3D) genome architecture of CLL. Beyond its regulatory role, the DNA methylome contains imprints of the cellular origin and proliferative history of CLL cells. These two aspects are strong independent prognostic factors. Integrative analyses of chromatin marks have uncovered novel regulatory elements and altered transcription factor networks as non-genetic means mediating gene deregulation in CLL. Additionally, CLL cells display a disease-specific pattern of 3D genome interactions. From the technological perspective, we are currently witnessing a transition from bulk omics to single-cell analyses. This review aims at summarising the major findings from the epigenomics field as well as providing a prospect of the present and future of single-cell analyses in CLL.]]>
Wed, 31 Dec 1969 19:00:00 EST
Epigenomic charting and functional annotation of risk loci in renal cell carcinoma. Nassar AH, Abou Alaiwi S, Baca SC, Adib E, Corona RI, Seo JH, Fonseca MAS, Spisak S, El Zarif T, Tisza V, Braun DA, Du H, He M, Flaifel A, Alchoueiry M, Denize T, Matar SG, Acosta A, Shukla S, Hou Y, Steinharter J, Bouchard G, Berchuck JE, O'Connor E, Bell C, Nuzzo PV, Mary Lee GS, Signoretti S, Hirsch MS, Pomerantz M, Henske E, Gusev A, Lawrenson K, Choueiri TK, Kwiatkowski DJ, Freedman ML
Nat Commun (Jan 2023)

While the mutational and transcriptional landscapes of renal cell carcinoma (RCC) are well-known, the epigenome is poorly understood. We characterize the epigenome of clear cell (ccRCC), papillary (pRCC), and chromophobe RCC (chRCC) by using ChIP-seq, ATAC-Seq, RNA-seq, and SNP arrays. We integrate 153 individual data sets from 42 patients and nominate 50 histology-specific master transcription factors (MTF) to define RCC histologic subtypes, including EPAS1 and ETS-1 in ccRCC, HNF1B in pRCC, and FOXI1 in chRCC. We confirm histology-specific MTFs via immunohistochemistry including a ccRCC-specific TF, BHLHE41. FOXI1 overexpression with knock-down of EPAS1 in the 786-O ccRCC cell line induces transcriptional upregulation of chRCC-specific genes, TFCP2L1, ATP6V0D2, KIT, and INSRR, implicating FOXI1 as a MTF for chRCC. Integrating RCC GWAS risk SNPs with H3K27ac ChIP-seq and ATAC-seq data reveals that risk-variants are significantly enriched in allelically-imbalanced peaks. This epigenomic atlas in primary human samples provides a resource for future investigation.]]>
Wed, 31 Dec 1969 19:00:00 EST
Transcriptomic, Epigenomic, and Neuroanatomic Signatures Differ in Chronic Prurigo, Atopic Dermatitis, and Brachioradial Pruritus. Agelopoulos K, Renkhold L, Wiegmann H, Dugas M, Süer A, Zeidler C, Schmelz M, Pereira MP, Ständer S
J Invest Dermatol (Feb 2023)

Scratching and scratch-induced injuries, including neuroanatomical alterations, are key characteristics of chronic pruritus entities of different origins. The aim of this study was to link gene expression (array hybridization, qPCR) with DNA methylation (array hybridization) and neuroanatomy (PGP9.5 staining) in chronic nodular prurigo (CNPG), atopic dermatitis (AD), brachioradial pruritus (BRP), and matched healthy controls. Specific signatures of gene expression and DNA methylation clearly discriminated pruritic lesional skin from nonpruritic skin in CNPG and from healthy skin of volunteers, respectively. Although intraepidermal nerve fiber density was indiscriminately reduced, the level of epidermal branching, assessed by a semiquantitative pattern analysis, differentiated the entities (CNPG > BRP > AD). Correspondingly, repellent SEMA3A showed the highest expression in AD, whereas axonal growth-promoting nerve GF was most prominent in CNPG and BRP. Overexpression of genes for nerve fiber regeneration (NELL2/NFKB/ARTN) was found in AD and CNPG but not in BRP. Our findings suggest that differential branching patterns rather than mere innervation density separate chronic itch conditions and reflect disease-specific local expression profiles. In pruritic dermatoses (AD and CNPG), nerve injury and subsequent sprouting may primarily result from chronic scratching, whereas genuine neuropathy is expected to underlie BRP.]]>
Wed, 31 Dec 1969 19:00:00 EST
Diffuse midline glioma treated with epigenetic agent-based immunotherapy. Jing L, Qian Z, Gao Q, Sun R, Zhen Z, Wang G, Yang X, Li H, Guo T, Zhang W
Signal Transduct Target Ther (Jan 2023)

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Wed, 31 Dec 1969 19:00:00 EST