scholarly journals DNA Demethylation Pathways: Recent Insights

2013 ◽  
Vol 5 ◽  
pp. GEG.S12143 ◽  
Author(s):  
Cong-jun Li
Keyword(s):  
Dna Methylation ◽  
Mammalian Cells ◽  
De Novo ◽  
Dna Demethylation ◽  
Epigenetic Mark ◽  
Sequencing Technologies ◽  
Active Dna Demethylation ◽  
Mammalian Genomes ◽  
Genome Context

DNA methylation is a major epigenetic regulatory mechanism for gene expression and cell differentiation. Until recently, it was still unclear how unmethylated regions in mammalian genomes are protected from de novo methylation and whether or not active demethylating activity is involved. Even the role of molecules and the mechanisms underlying the processes of active demethylation itself is blurred. Emerging sequencing technologies have led to recent insights into the dynamic distribution of DNA methylation during development and the role of this epigenetic mark within a distinct genome context, such as the promoters, exons, or imprinted control regions. This review summarizes recent insights on the dynamic nature of DNA methylation and demethylation, as well as the mechanisms regulating active DNA demethylation in mammalian cells, which have been fundamental research interests in the field of epigenomics.

scholarly journals DNA methylation dynamics during the mammalian life cycle

2013 ◽  
Vol 368 (1609) ◽  
pp. 20110328 ◽  
Author(s):  
Jamie A. Hackett ◽  
M. Azim Surani
Keyword(s):  
Dna Methylation ◽  
Life Cycle ◽  
Genome Stability ◽  
De Novo ◽  
Primordial Germ Cells ◽  
Dna Demethylation ◽  
Epigenetic Mark ◽  
Sequencing Technologies ◽  
Mechanistic Basis ◽  
Successive Generations

DNA methylation is dynamically remodelled during the mammalian life cycle through distinct phases of reprogramming and de novo methylation. These events enable the acquisition of cellular potential followed by the maintenance of lineage-restricted cell identity, respectively, a process that defines the life cycle through successive generations. DNA methylation contributes to the epigenetic regulation of many key developmental processes including genomic imprinting, X-inactivation, genome stability and gene regulation. Emerging sequencing technologies have led to recent insights into the dynamic distribution of DNA methylation during development and the role of this epigenetic mark within distinct genomic contexts, such as at promoters, exons or imprinted control regions. Additionally, there is a better understanding of the mechanistic basis of DNA demethylation during epigenetic reprogramming in primordial germ cells and during pre-implantation development. Here, we discuss our current understanding of the developmental roles and dynamics of this key epigenetic system.

scholarly journals RNA sequencing-based screen for reactivation of silenced alleles of autosomal genes

2021 ◽  
Author(s):  
Saumya Gupta ◽  
Denis L Lafontaine ◽  
Sebastien Vigneau ◽  
Asia Mendelevich ◽  
Svetlana Vinogradova ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Rna Sequencing ◽  
Mammalian Cells ◽  
Allelic Imbalance ◽  
Dna Demethylation ◽  
Monoallelic Expression ◽  
Specific Expression ◽  
Allele Specific ◽  
Mechanistic Basis

Abstract In mammalian cells, maternal and paternal alleles usually have similar transcriptional activity. Epigenetic mechanisms such as X-chromosome inactivation (XCI) and imprinting were historically viewed as rare exceptions to this rule. Discovery of autosomal monoallelic expression (MAE) a decade ago revealed an additional allele-specific mode regulating thousands of mammalian genes. Despite MAE prevalence, its mechanistic basis remains unknown. Using an RNA sequencing-based screen for reactivation of silenced alleles, we identified DNA methylation as key mechanism of MAE mitotic maintenance. In contrast with the all-or-nothing allelic choice in XCI, allele-specific expression in MAE loci is tunable, with exact allelic imbalance dependent on the extent of DNA methylation. In a subset of MAE genes, allelic imbalance was insensitive to DNA demethylation, implicating additional mechanisms in MAE maintenance in these loci. Our findings identify a key mechanism of MAE maintenance and provide basis for understanding the biological role of MAE.

scholarly journals Direct decarboxylation of Ten-eleven translocation-produced 5-carboxylcytosine in mammalian genomes forms a new mechanism for active DNA demethylation

2021 ◽  
Author(s):  
Yang Feng ◽  
Juan-Juan Chen ◽  
Neng-Bin Xie ◽  
Jiang-Hui Ding ◽  
Xue-Jiao You ◽  
...  
Keyword(s):  
Cytosine Methylation ◽  
Dna Demethylation ◽  
Epigenetic Mark ◽  
Active Dna Demethylation ◽  
Mammalian Genomes ◽  
Higher Eukaryotes ◽  
Dna Cytosine Methylation

DNA cytosine methylation (5-methylcytosine, 5mC) is the most important epigenetic mark in higher eukaryotes. 5mC in genomes is dynamically controlled by the writers and erasers. DNA (cytosine-5)-methyltransferases (DNMTs) are responsible...

scholarly journals Critical roles of DNA demethylation in the activation of ripening-induced genes and inhibition of ripening-repressed genes in tomato fruit

2017 ◽  
Vol 114 (22) ◽  
pp. E4511-E4519 ◽  
Author(s):  
Zhaobo Lang ◽  
Yihai Wang ◽  
Kai Tang ◽  
Dengguo Tang ◽  
Tatsiana Datsenka ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Fruit Ripening ◽  
Tomato Fruit ◽  
Dna Demethylation ◽  
Epigenetic Mark ◽  
Loss Of Function ◽  
Active Dna Demethylation ◽  
Tomato Fruit Ripening ◽  
Induced Genes ◽  
Environmental Responses

DNA methylation is a conserved epigenetic mark important for genome integrity, development, and environmental responses in plants and mammals. Active DNA demethylation in plants is initiated by a family of 5-mC DNA glycosylases/lyases (i.e., DNA demethylases). Recent reports suggested a role of active DNA demethylation in fruit ripening in tomato. In this study, we generated loss-of-function mutant alleles of a tomato gene, SlDML2, which is a close homolog of the Arabidopsis DNA demethylase gene ROS1. In the fruits of the tomato mutants, increased DNA methylation was found in thousands of genes. These genes included not only hundreds of ripening-induced genes but also many ripening-repressed genes. Our results show that SlDML2 is critical for tomato fruit ripening and suggest that active DNA demethylation is required for both the activation of ripening-induced genes and the inhibition of ripening-repressed genes.

scholarly journals Tet proteins: on track towards DNA demethylation?

2012 ◽  
Vol 3 (5) ◽  
pp. 395-402 ◽  
Author(s):  
Nathalie Véron
Keyword(s):  
Dna Methylation ◽  
Enzymatic Activity ◽  
Dna Demethylation ◽  
Epigenetic Mark ◽  
Developmental Processes ◽  
Tet Proteins ◽  
Active Dna Demethylation ◽  
Demethylation Pathway ◽  
Cellular Integrity ◽  
Tet Protein

AbstractDynamic DNA methylation is a prerequisite for many developmental processes and maintenance of cellular integrity. In mammals however, mechanisms of active DNA demethylation have for long been elusive. The discovery of the ten-eleven translocation (Tet) family of enzymes that oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) or 5-carboxylcytosine (5caC) provided new means by which DNA methylation could actively be reversed. This review focuses on the possible mechanisms of DNA demethylation via Tet proteins and their metabolites 5hmC, 5fC and 5caC. Additionally, it discusses the roles of the three Tet protein family members Tet1, Tet2 and Tet3 as developmental regulators, probably in part independent of their enzymatic activity. By contrast, recent evidence suggests a function of 5hmC as an epigenetic mark on its own, going beyond the expectation of only acting as an intermediate in an active DNA demethylation pathway.

scholarly journals Active DNA demethylation regulates tracheary element differentiation in Arabidopsis

2020 ◽  
Vol 6 (26) ◽  
pp. eaaz2963
Author(s):  
Wei Lin ◽  
Linhua Sun ◽  
Run-Zhou Huang ◽  
Wenjie Liang ◽  
Xinyu Liu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Tracheary Element ◽  
Dna Demethylation ◽  
Epigenetic Mechanism ◽  
Dna Glycosylases ◽  
Tracheary Element Differentiation ◽  
Xylem Development ◽  
Active Dna Demethylation ◽  
Genomic Regions

DNA demethylation is important for the erasure of DNA methylation. The role of DNA demethylation in plant development remains poorly understood. Here, we found extensive DNA demethylation in the CHH context around pericentromeric regions and DNA demethylation in the CG, CHG, and CHH contexts at discrete genomic regions during ectopic xylem tracheary element (TE) differentiation. While loss of pericentromeric methylation occurs passively, DNA demethylation at a subset of regions relies on active DNA demethylation initiated by DNA glycosylases ROS1, DML2, and DML3. The ros1 and rdd mutations impair ectopic TE differentiation and xylem development in the young roots of Arabidopsis seedlings. Active DNA demethylation targets and regulates many genes for TE differentiation. The defect of xylem development in rdd is proposed to be caused by dysregulation of multiple genes. Our study identifies a role of active DNA demethylation in vascular development and reveals an epigenetic mechanism for TE differentiation.

scholarly journals Regulatory link between DNA methylation and active demethylation in Arabidopsis

2015 ◽  
Vol 112 (11) ◽  
pp. 3553-3557 ◽  
Author(s):  
Mingguang Lei ◽  
Huiming Zhang ◽  
Russell Julian ◽  
Kai Tang ◽  
Shaojun Xie ◽  
...  
Keyword(s):  
Dna Methylation ◽  
De Novo ◽  
Gene Promoter ◽  
Dna Demethylation ◽  
Target Sequence ◽  
Loss Of Function ◽  
Dna Hypermethylation ◽  
Active Demethylation ◽  
Active Dna Demethylation ◽  
Regulatory Link

De novo DNA methylation through the RNA-directed DNA methylation (RdDM) pathway and active DNA demethylation play important roles in controlling genome-wide DNA methylation patterns in plants. Little is known about how cells manage the balance between DNA methylation and active demethylation activities. Here, we report the identification of a unique RdDM target sequence, where DNA methylation is required for maintaining proper active DNA demethylation of the Arabidopsis genome. In a genetic screen for cellular antisilencing factors, we isolated several REPRESSOR OF SILENCING 1 (ros1) mutant alleles, as well as many RdDM mutants, which showed drastically reduced ROS1 gene expression and, consequently, transcriptional silencing of two reporter genes. A helitron transposon element (TE) in the ROS1 gene promoter negatively controls ROS1 expression, whereas DNA methylation of an RdDM target sequence between ROS1 5′ UTR and the promoter TE region antagonizes this helitron TE in regulating ROS1 expression. This RdDM target sequence is also targeted by ROS1, and defective DNA demethylation in loss-of-function ros1 mutant alleles causes DNA hypermethylation of this sequence and concomitantly causes increased ROS1 expression. Our results suggest that this sequence in the ROS1 promoter region serves as a DNA methylation monitoring sequence (MEMS) that senses DNA methylation and active DNA demethylation activities. Therefore, the ROS1 promoter functions like a thermostat (i.e., methylstat) to sense DNA methylation levels and regulates DNA methylation by controlling ROS1 expression.

scholarly journals Global increase in DNA methylation during orange fruit development and ripening

2019 ◽  
Vol 116 (4) ◽  
pp. 1430-1436 ◽  
Author(s):  
Huan Huang ◽  
Ruie Liu ◽  
Qingfeng Niu ◽  
Kai Tang ◽  
Bo Zhang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Fruit Ripening ◽  
Tomato Fruit ◽  
Dna Demethylation ◽  
Epigenetic Mark ◽  
Dna Hypermethylation ◽  
Active Dna Demethylation ◽  
Orange Fruit ◽  
Global Increase ◽  
Genomic Regions

DNA methylation is an important epigenetic mark involved in many biological processes. The genome of the climacteric tomato fruit undergoes a global loss of DNA methylation due to active DNA demethylation during the ripening process. It is unclear whether the ripening of other fruits is also associated with global DNA demethylation. We characterized the single-base resolution DNA methylomes of sweet orange fruits. Compared with immature orange fruits, ripe orange fruits gained DNA methylation at over 30,000 genomic regions and lost DNA methylation at about 1,000 genomic regions, suggesting a global increase in DNA methylation during orange fruit ripening. This increase in DNA methylation was correlated with decreased expression of DNA demethylase genes. The application of a DNA methylation inhibitor interfered with ripening, indicating that the DNA hypermethylation is critical for the proper ripening of orange fruits. We found that ripening-associated DNA hypermethylation was associated with the repression of several hundred genes, such as photosynthesis genes, and with the activation of hundreds of genes, including genes involved in abscisic acid responses. Our results suggest important roles of DNA methylation in orange fruit ripening.

scholarly journals Photodamage repair pathways contribute to the accurate maintenance of the DNA methylome landscape upon UV exposure

2019 ◽  
Author(s):  
Stéfanie Graindorge ◽  
Valérie Cognat ◽  
Philippe Johann to Berens ◽  
Jérôme Mutterer ◽  
Jean Molinier
Keyword(s):  
Dna Methylation ◽  
Dna Repair ◽  
De Novo ◽  
Dna Demethylation ◽  
Dna Lesions ◽  
Active Dna Demethylation ◽  
Repair Pathways ◽  
Dna Photolesions ◽  
Genomic Regions ◽  
Uv C

AbstractPlants are exposed to the damaging effect of sunlight that induces DNA photolesions. In order to maintain genome integrity, specific DNA repair pathways are mobilized. Upon removal of UV-induced DNA lesions, the accurate re-establishment of epigenome landscape is expected to be a prominent step of these DNA repair pathways. However, it remains poorly documented whether DNA methylation is accurately maintained at photodamaged sites and how photodamage repair pathways contribute to the maintenance of genome/methylome integrities. Using genome wide approaches, we report that UV-C irradiation leads to asymmetric DNA methylation changes. We identified that the specific DNA repair pathways involved in the repair of UV-induced DNA lesions, Direct Repair (DR) and Global Genome Repair (GGR), prevent the excessive alterations of DNA methylation landscape. Moreover, we identified that UV-C irradiation induced chromocenter reorganization and that photodamage repair factors control this dynamics. The methylome changes rely on misregulation of maintenance, de novo and active DNA demethylation pathways highlighting that molecular processes related to genome and methylome integrities are closely interconnected. Importantly, we identified that photolesions are sources of DNA methylation changes in both, constitutive and facultative heterochromatin. This study unveils that DNA repair factors, together with small RNA, act to accurately maintain both genome and methylome integrities at photodamaged silent genomic regions, strengthening the idea that plants have evolved sophisticated interplays between DNA methylation dynamics and DNA repair.

scholarly journals Application of 5-Methylcytosine DNA Glycosylase to the Quantitative Analysis of DNA Methylation

2021 ◽  
Vol 22 (3) ◽  
pp. 1072
Author(s):  
Woo Lee Choi ◽  
Young Geun Mok ◽  
Jin Hoe Huh
Keyword(s):  
Dna Methylation ◽  
Strand Break ◽  
Dna Methyltransferases ◽  
Dna Demethylation ◽  
Dna Glycosylase ◽  
Epigenetic Mark ◽  
Gene Expressions ◽  
Independent Manner ◽  
Single Strand Break ◽  
Active Dna Demethylation

In higher eukaryotes DNA methylation is a prominent epigenetic mark important for chromatin structure and gene expression. Thus, profiling DNA methylation is important for predicting gene expressions associated with specific traits or diseases. DNA methylation is achieved by DNA methyltransferases and can be actively removed by specific enzymes in a replication-independent manner. DEMETER (DME) is a bifunctional 5-methylcytosine (5mC) DNA glycosylase responsible for active DNA demethylation that excises 5mC from DNA and cleaves a sugar-phosphate bond generating a single strand break (SSB). In this study, DME was used to analyze DNA methylation levels at specific epialleles accompanied with gain or loss of DNA methylation. DME treatment on genomic DNA generates SSBs in a nonsequence-specific fashion proportional to 5mC density, and thus DNA methylation levels can be easily measured when combined with the quantitative PCR (qPCR) method. The DME-qPCR analysis was applied to measure DNA methylation levels at the FWA gene in late-flowering Arabidopsis mutants and the CNR gene during fruit ripening in tomato. Differentially methylated epialleles were successfully distinguished corresponding to their expression levels and phenotypes. DME-qPCR is proven a simple yet effective method for quantitative DNA methylation analysis, providing advantages over current techniques based on methylation-sensitive restriction digestion.

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