keyword
https://read.qxmd.com/read/38190722/unusual-predominance-of-maintenance-dna-methylation-in-spirodela-polyrhiza
#21
JOURNAL ARTICLE
Alex Harkess, Adam J Bewick, Zefu Lu, Paul Fourounjian, Todd P Michael, Robert J Schmitz, Blake C Meyers
Duckweeds are among the fastest reproducing plants, able to clonally divide at exponential rates. However, the genetic and epigenetic impact of clonality on plant genomes is poorly understood. 5-methylcytosine (5mC) is a modified base often described as necessary for the proper regulation of certain genes and transposons and for the maintenance of genome integrity in plants. However, the extent of this dogma is limited by the current phylogenetic sampling of land plant species diversity. Here we analyzed DNA methylomes, small RNAs, mRNA-seq, and H3K9me2 histone modification for Spirodela polyrhiza...
January 8, 2024: G3: Genes—Genomes—Genetics
https://read.qxmd.com/read/38136671/using-selective-enzymes-to-measure-noncanonical-dna-building-blocks-dutp-5-methyl-dctp-and-5-hydroxymethyl-dctp
#22
JOURNAL ARTICLE
Éva Viola Surányi, Viktória Perey-Simon, Rita Hirmondó, Tamás Trombitás, Latifa Kazzazy, Máté Varga, Beáta G Vértessy, Judit Tóth
Cells maintain a fine-tuned balance of deoxyribonucleoside 5'-triphosphates (dNTPs), a crucial factor in preserving genomic integrity. Any alterations in the nucleotide pool's composition or chemical modifications to nucleotides before their incorporation into DNA can lead to increased mutation frequency and DNA damage. In addition to the chemical modification of canonical dNTPs, the cellular de novo dNTP metabolism pathways also produce noncanonical dNTPs. To keep their levels low and prevent them from incorporating into the DNA, these noncanonical dNTPs are removed from the dNTP pool by sanitizing enzymes...
December 15, 2023: Biomolecules
https://read.qxmd.com/read/38136588/icf1-syndrome-associated-dnmt3b-mutations-prevent-de-novo-methylation-at-a-subset-of-imprinted-loci-during-ipsc-reprogramming
#23
JOURNAL ARTICLE
Ankit Verma, Varsha Poondi Krishnan, Francesco Cecere, Emilia D'Angelo, Vincenzo Lullo, Maria Strazzullo, Sara Selig, Claudia Angelini, Maria R Matarazzo, Andrea Riccio
Parent-of-origin-dependent gene expression of a few hundred human genes is achieved by differential DNA methylation of both parental alleles. This imprinting is required for normal development, and defects in this process lead to human disease. Induced pluripotent stem cells (iPSCs) serve as a valuable tool for in vitro disease modeling. However, a wave of de novo DNA methylation during reprogramming of iPSCs affects DNA methylation, thus limiting their use. The DNA methyltransferase 3B ( DNMT3B ) gene is highly expressed in human iPSCs; however, whether the hypermethylation of imprinted loci depends on DNMT3B activity has been poorly investigated...
November 28, 2023: Biomolecules
https://read.qxmd.com/read/38108041/detection-of-modified-histones-from-oral-mucosa-of-a-patient-with-dyt-kmt2b-dystonia
#24
JOURNAL ARTICLE
Naoto Sugeno, Takafumi Hasegawa, Kazuhiro Haginoya, Takafumi Kubota, Kensuke Ikeda, Takaaki Nakamura, Shun Ishiyama, Kazuki Sato, Shun Yoshida, Eriko Koshimizu, Mitsugu Uematsu, Satoko Miyatake, Naomichi Matsumoto, Masashi Aoki
INTRODUCTION: DYT- KMT2B is a rare childhood-onset, hereditary movement disorder typically characterized by lower-limb dystonia and subsequently spreads into the craniocervical and laryngeal muscles. Recently, KMT2B -encoding lysine (K)-specific histone methyltransferase 2B was identified as the causative gene for DYT- KMT2B , also known as DYT28. In addition to the fact that many physicians do not have sufficient experience or knowledge of hereditary dystonia, the clinical features of DYT- KMT2B overlap with those of other hereditary dystonia, and limited clinical biomarkers make the diagnosis difficult...
December 2023: Molecular Syndromology
https://read.qxmd.com/read/38105210/response-of-primpol-knockout-human-lung-adenocarcinoma-a549-cells-to-genotoxic-stress
#25
JOURNAL ARTICLE
Anastasia S Gromova, Elizaveta O Boldinova, Daria V Kim, Roman N Chuprov-Netochin, Sergey V Leonov, Margarita V Pustovalova, Dmitry O Zharkov, Alena V Makarova
Human DNA primase/polymerase PrimPol synthesizes DNA primers de novo after replication fork stalling at the sites of DNA damage, thus contributing to the DNA damage tolerance. The role of PrimPol in response to the different types of DNA damage is poorly understood. We knocked out the PRIMPOL gene in the lung carcinoma A549 cell line and characterized the response of the obtained cells to the DNA damage caused by hydrogen peroxide, methyl methanesulfonate (MMS), cisplatin, bleomycin, and ionizing radiation...
November 2023: Biochemistry. Biokhimii︠a︡
https://read.qxmd.com/read/38084599/macromolecular-complex-including-mll3-carabin-and-calcineurin-regulates-cardiac-remodeling
#26
JOURNAL ARTICLE
Roberto Pane, Loubna Laib, Karina Formoso, Maximin Détrait, Yannis Sainte-Marie, Florence Bourgailh, Nolan Ruffenach, Hanamée Faugeras, Ilias Simon, Emeline Lhuillier, Frank Lezoualc'h, Caroline Conte
BACKGROUND: Cardiac hypertrophy is an intermediate stage in the development of heart failure. The structural and functional processes occurring in cardiac hypertrophy include extensive gene reprogramming, which is dependent on epigenetic regulation and chromatin remodeling. However, the chromatin remodelers and their regulatory functions involved in the pathogenesis of cardiac hypertrophy are not well characterized. METHODS: Protein interaction was determined by immunoprecipitation assay in primary cardiomyocytes and mouse cardiac samples subjected or not to transverse aortic constriction for 1 week...
January 5, 2024: Circulation Research
https://read.qxmd.com/read/38079020/-de-novo-replication-repair-deficient-glioblastoma-idh-wildtype-is-a-distinct-glioblastoma-subtype-in-adults-that-may-benefit-from-immune-checkpoint-blockade
#27
JOURNAL ARTICLE
Sara Hadad, Rohit Gupta, Nancy Ann Oberheim Bush, Jennie W Taylor, Javier E Villanueva-Meyer, Jacob S Young, Jasper Wu, Ajay Ravindranathan, Yalan Zhang, Gayathri Warrier, Lucie McCoy, Anny Shai, Melike Pekmezci, Arie Perry, Andrew W Bollen, Joanna J Phillips, Steve E Braunstein, David R Raleigh, Philip Theodosopoulos, Manish K Aghi, Edward F Chang, Shawn L Hervey-Jumper, Joseph F Costello, John de Groot, Nicholas A Butowski, Jennifer L Clarke, Susan M Chang, Mitchel S Berger, Annette M Molinaro, David A Solomon
Glioblastoma is a clinically and molecularly heterogeneous disease, and new predictive biomarkers are needed to identify those patients most likely to respond to specific treatments. Through prospective genomic profiling of 459 consecutive primary treatment-naïve IDH-wildtype glioblastomas in adults, we identified a unique subgroup (2%, 9/459) defined by somatic hypermutation and DNA replication repair deficiency due to biallelic inactivation of a canonical mismatch repair gene. The deleterious mutations in mismatch repair genes were often present in the germline in the heterozygous state with somatic inactivation of the remaining allele, consistent with glioblastomas arising due to underlying Lynch syndrome...
December 11, 2023: Acta Neuropathologica
https://read.qxmd.com/read/38076935/differential-cpg-methylation-at-nnat-in-the-early-establishment-of-beta-cell-heterogeneity
#28
Vanessa Yu, Fiona Yong, Angellica Marta, Sanjay Khadayate, Adrien Osakwe, Supriyo Bhattacharya, Sneha S Varghese, Pauline Chabosseau, Sayed M Tabibi, Keran Chen, Eleni Georgiadou, Nazia Parveen, Mara Suleiman, Zoe Stamoulis, Lorella Marselli, Carmela De Luca, Marta Tesi, Giada Ostinelli, Luis Delgadillo-Silva, Xiwei Wu, Yuki Hatanaka, Alex Montoya, James Elliott, Bhavik Patel, Nikita Demchenko, Chad Whilding, Petra Hajkova, Pavel Shliaha, Holger Kramer, Yusuf Ali, Piero Marchetti, Robert Sladek, Sangeeta Dhawan, Dominic J Withers, Guy A Rutter, Steven J Millership
AIMS/HYPOTHESIS: Beta cells within the pancreatic islet represent a heterogenous population wherein individual sub-groups of cells make distinct contributions to the overall control of insulin secretion. These include a subpopulation of highly-connected 'hub' cells, important for the propagation of intercellular Ca 2+ waves. Functional subpopulations have also been demonstrated in human beta cells, with an altered subtype distribution apparent in type 2 diabetes. At present, the molecular mechanisms through which beta cell hierarchy is established are poorly understood...
November 30, 2023: bioRxiv
https://read.qxmd.com/read/38069050/g6pd-orchestrates-genome-wide-dna-methylation-and-gene-expression-in-the-vascular-wall
#29
JOURNAL ARTICLE
Christina Signoretti, Sachin A Gupte
Recent advances have revealed the importance of epigenetic modifications to gene regulation and transcriptional activity. DNA methylation, a determinant of genetic imprinting and the de novo silencing of genes genome-wide, is known to be controlled by DNA methyltransferases (DNMT) and demethylases (TET) under disease conditions. However, the mechanism(s)/factor(s) influencing the expression and activity of epigenetic writers and erasers, and thus DNA methylation, in healthy vascular tissue is incompletely understood...
November 24, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/38049411/nitric-oxide-controls-shoot-meristem-activity-via-regulation-of-dna-methylation
#30
JOURNAL ARTICLE
Jian Zeng, Xin'Ai Zhao, Zhe Liang, Inés Hidalgo, Michael Gebert, Pengfei Fan, Christian Wenzl, Sebastian G Gornik, Jan U Lohmann
Despite the importance of Nitric Oxide (NO) as signaling molecule in both plant and animal development, the regulatory mechanisms downstream of NO remain largely unclear. Here, we show that NO is involved in Arabidopsis shoot stem cell control via modifying expression and activity of ARGONAUTE 4 (AGO4), a core component of the RNA-directed DNA Methylation (RdDM) pathway. Mutations in components of the RdDM pathway cause meristematic defects, and reduce responses of the stem cell system to NO signaling...
December 4, 2023: Nature Communications
https://read.qxmd.com/read/38033464/epigenetics-mechanisms-of-honeybees-secrets-of-royal-jelly
#31
REVIEW
Mahmoud Alhosin
Early diets in honeybees have effects on epigenome with consequences on their phenotype. Depending on the early larval diet, either royal jelly (RJ) or royal worker, 2 different female castes are generated from identical genomes, a long-lived queen with fully developed ovaries and a short-lived functionally sterile worker. To generate these prominent physiological and morphological differences between queen and worker, honeybees utilize epigenetic mechanisms which are controlled by nutritional input. These mechanisms include DNA methylation and histone post-translational modifications, mainly histone acetylation...
2023: Epigenetics Insights
https://read.qxmd.com/read/37994961/alox5ap-is-a-new-prognostic-indicator-in-acute-myeloid-leukemia
#32
JOURNAL ARTICLE
Xin-Yi Chen, Xiang-Mei Wen, Wei Zhao, Ming-Qiang Chu, Yu Gu, Hai-Hui Huang, Qian Yuan, Zi-Jun Xu, Jun Qian, Jiang Lin
BACKGROUND: The overexpression of ALOX5AP has been observed in many types of cancer and has been identified as an oncogene. However, its role in acute myeloid leukemia (AML) has not been extensively studied. This study aimed to identify the expression and methylation patterns of ALOX5AP in bone marrow (BM) samples of AML patients, and further explore its clinical significance. METHODS: Eighty-two de novo AML patients and 20 healthy donors were included in the study...
November 23, 2023: Discover. Oncology
https://read.qxmd.com/read/37994176/loss-of-dna-methylation-disrupts-syncytiotrophoblast-development-proposed-consequences-of-aberrant-germline-gene-activation
#33
JOURNAL ARTICLE
Georgia Lea, Courtney W Hanna
DNA methylation is a repressive epigenetic modification that is essential for development and its disruption is widely implicated in disease. Yet, remarkably, ablation of DNA methylation in transgenic mouse models has limited impact on transcriptional states. Across multiple tissues and developmental contexts, the predominant transcriptional signature upon loss of DNA methylation is the de-repression of a subset of germline genes, normally expressed in gametogenesis. We recently reported loss of de novo DNA methyltransferase DNMT3B resulted in up-regulation of germline genes and impaired syncytiotrophoblast formation in the murine placenta...
November 22, 2023: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://read.qxmd.com/read/37992039/rice-requires-a-chromatin-remodeler-for-polymerase-iv-small-interfering-rna-production-and-genomic-immunity
#34
JOURNAL ARTICLE
Dachao Xu, Longjun Zeng, Lili Wang, Dong-Lei Yang
Transgenes are often spontaneously silenced, which hinders the application of genetic modifications to crop breeding. While gene silencing has been extensively studied in Arabidopsis (Arabidopsis thaliana), the molecular mechanism of transgene silencing remains elusive in crop plants. We used rice (Oryza sativa) plants silenced for a 35S::OsGA2ox1 (Gibberellin 2-oxidase 1) transgene to isolate five elements mountain (fem) mutants showing restoration of transgene expression. In this study, we isolated multiple fem2 mutants defective in a homolog of Required to Maintain Repression 1 (RMR1) of maize (Zea mays) and CLASSY (CLSY) of Arabidopsis...
November 22, 2023: Plant Physiology
https://read.qxmd.com/read/37987565/mating-system-is-associated-with-seed-phenotypes-upon-loss-of-rna-directed-dna-methylation-in-brassicaceae
#35
JOURNAL ARTICLE
Kelly J Dew-Budd, Hiu Tung Chow, Timmy Kendall, Brandon C David, James A Rozelle, Rebecca A Mosher, Mark A Beilstein
In plants, de novo DNA methylation is guided by 24-nt short interfering (si)RNAs in a process called RNA-directed DNA methylation (RdDM). Primarily targeted at transposons, RdDM causes transcriptional silencing and can indirectly influence expression of neighboring genes. During reproduction, a small number of siRNA loci are dramatically upregulated in the maternally-derived seed coat, suggesting that RdDM might have a special function during reproduction. However, the developmental consequence of RdDM has been difficult to dissect because disruption of RdDM does not result in overt phenotypes in Arabidopsis (Arabidopsis thaliana), where the pathway has been most thoroughly studied...
November 21, 2023: Plant Physiology
https://read.qxmd.com/read/37984997/a-naturally-occurring-variant-of-mbd4-causes-maternal-germline-hypermutation-in-primates
#36
JOURNAL ARTICLE
Alexandra M Stendahl, Rashesh Sanghvi, Samuel Peterson, Karina Ray, Ana C Lima, Raheleh Rahbari, Donald F Conrad
As part of an ongoing genome sequencing project at the Oregon National Primate Research Center, we identified a rhesus macaque with a rare homozygous frameshift mutation in the gene methyl-CpG binding domain 4, DNA glycosylase ( MBD4 ). MBD4 is responsible for the repair of C > T deamination mutations at CpG dinucleotides and has been linked to somatic hypermutation and cancer predisposition in humans. We show here that MBD4-associated hypermutation also affects the germline: The six offspring of the MBD4 -null dam have a fourfold to sixfold increase in de novo mutation burden...
December 8, 2023: Genome Research
https://read.qxmd.com/read/37970883/identification-of-a-novel-epigenetic-marker-for-typical-and-mosaic-presentations-of-fragile-x-syndrome
#37
JOURNAL ARTICLE
Camilla Pereira da Silva, Diego Camuzi, Adriana Helena Deliveira Reis, Andressa Pereira Gonçalves, Jussara Mendonça Dos Santos, Filipe Brum Machado, Enrique Medina-Acosta, Sheila Coelho Soares-Lima, Cíntia Barros Santos-Rebouças
BACKGROUND: Fragile X syndrome (FXS) is primarily due to CGG repeat expansions in the FMR1 gene. FMR1 alleles are classified as normal (N), intermediate (I), premutation (PM), and full mutation (FM). FXS patients often carry an FM, but size mosaicism can occur. Additionally, loss of methylation boundary upstream of repeats results in de novo methylation spreading to FMR1 promoter in FXS patients. RESEARCH DESIGN AND METHODS: This pilot study investigated the methylation boundary and adjacent regions in 66 males with typical and atypical FXS aged 1 to 30 years (10...
November 16, 2023: Expert Review of Molecular Diagnostics
https://read.qxmd.com/read/37947606/the-role-of-clonal-hematopoiesis-of-indeterminant-potential-and-dna-cytosine-5-methyltransferase-dysregulation-in-pulmonary-arterial-hypertension-and-other-cardiovascular-diseases
#38
REVIEW
Isaac M Emon, Ruaa Al-Qazazi, Michael J Rauh, Stephen L Archer
DNA methylation is an epigenetic mechanism that regulates gene expression without altering gene sequences in health and disease. DNA methyltransferases (DNMTs) are enzymes responsible for DNA methylation, and their dysregulation is both a pathogenic mechanism of disease and a therapeutic target. DNMTs change gene expression by methylating CpG islands within exonic and intergenic DNA regions, which typically reduces gene transcription. Initially, mutations in the DNMT genes and pathologic DNMT protein expression were found to cause hematologic diseases, like myeloproliferative disease and acute myeloid leukemia, but recently they have been shown to promote cardiovascular diseases, including coronary artery disease and pulmonary hypertension...
October 26, 2023: Cells
https://read.qxmd.com/read/37944515/millennia-long-epigenetic-fluctuations-generate-intragenic-dna-methylation-variance-in-arabidopsis-populations
#39
JOURNAL ARTICLE
Amy Briffa, Elizabeth Hollwey, Zaigham Shahzad, Jonathan D Moore, David B Lyons, Martin Howard, Daniel Zilberman
Methylation of CG dinucleotides (mCGs), which regulates eukaryotic genome functions, is epigenetically propagated by Dnmt1/MET1 methyltransferases. How mCG is established and transmitted across generations despite imperfect enzyme fidelity is unclear. Whether mCG variation in natural populations is governed by genetic or epigenetic inheritance also remains mysterious. Here, we show that MET1 de novo activity, which is enhanced by existing proximate methylation, seeds and stabilizes mCG in Arabidopsis thaliana genes...
November 3, 2023: Cell Systems
https://read.qxmd.com/read/37941146/structural-basis-for-the-allosteric-regulation-and-dynamic-assembly-of-dnmt3b
#40
JOURNAL ARTICLE
Jiuwei Lu, Jian Fang, Hongtao Zhu, Kimberly Lu Liang, Nelli Khudaverdyan, Jikui Song
Oligomerization of DNMT3B, a mammalian de novo DNA methyltransferase, critically regulates its chromatin targeting and DNA methylation activities. However, how the N-terminal PWWP and ADD domains interplay with the C-terminal methyltransferase (MTase) domain in regulating the dynamic assembly of DNMT3B remains unclear. Here, we report the cryo-EM structure of DNMT3B under various oligomerization states. The ADD domain of DNMT3B interacts with the MTase domain to form an autoinhibitory conformation, resembling the previously observed DNMT3A autoinhibition...
November 6, 2023: Nucleic Acids Research
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