scholarly journals The exploration of N6-deoxyadenosine methylation in mammalian genomes

2021 ◽  
Author(s):  
Xuwen Li ◽  
Zijian Zhang ◽  
Xinlong Luo ◽  
Jacob Schrier ◽  
Andrew D. Yang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Regulatory Mechanism ◽  
Epigenetic Mark ◽  
Dna Modification ◽  
Biological Processes ◽  
Environmental Stress Response ◽  
Mammalian Genomes ◽  
Higher Eukaryotes ◽  
And Function ◽  
Major Progress

AbstractN6-methyladenine (N6-mA, m6dA, or 6mA), a prevalent DNA modification in prokaryotes, has recently been identified in higher eukaryotes, including mammals. Although 6mA has been well-studied in prokaryotes, the function and regulatory mechanism of 6mA in eukaryotes are still poorly understood. Recent studies indicate that 6mA can serve as an epigenetic mark and play critical roles in various biological processes, from transposable-element suppression to environmental stress response. Here, we review the significant advances in methodology for 6mA detection and major progress in understanding the regulation and function of this non-canonical DNA methylation in eukaryotes, predominantly mammals.

scholarly journals DNA modifications in the mammalian brain

2014 ◽  
Vol 369 (1652) ◽  
pp. 20130512 ◽  
Author(s):  
Jaehoon Shin ◽  
Guo-li Ming ◽  
Hongjun Song
Keyword(s):  
Dna Methylation ◽  
Brain Development ◽  
Genomic Imprinting ◽  
Mammalian Brain ◽  
Epigenetic Mark ◽  
Mammalian Development ◽  
Dna Modifications ◽  
Dna Elements ◽  
And Function ◽  
Neuronal Functions

DNA methylation is a crucial epigenetic mark in mammalian development, genomic imprinting, X-inactivation, chromosomal stability and suppressing parasitic DNA elements. DNA methylation in neurons has also been suggested to play important roles for mammalian neuronal functions, and learning and memory. In this review, we first summarize recent discoveries and fundamental principles of DNA modifications in the general epigenetics field. We then describe the profiles of different DNA modifications in the mammalian brain genome. Finally, we discuss roles of DNA modifications in mammalian brain development and function.

scholarly journals Whole genome bisulfite sequencing reveals a sparse, but robust pattern of DNA methylation in the Dictyostelium discoideum genome

2017 ◽  
Author(s):  
Jacob L. Steenwyk ◽  
James St. Denis ◽  
Jacqueline M. Dresch ◽  
Denis A. Larochelle ◽  
Robert A. Drewell
Keyword(s):  
Dna Methylation ◽  
Dictyostelium Discoideum ◽  
Dna Methyltransferase ◽  
Model Organism ◽  
Epigenetic Mark ◽  
Whole Genome ◽  
Protein Coding ◽  
Genome Bisulfite Sequencing ◽  
Chromatin Structural ◽  
And Function

AbstractDNA methylation, the addition of a methyl (CH3) group to a cytosine residue, is an evolutionarily conserved epigenetic mark involved in a number of different biological functions in eukaryotes, including transcriptional regulation, chromatin structural organization, cellular differentiation and development. In the slime mold Dictyostelium, previous studies have shown the existence of a DNA methyltransferase (DNMA) belonging to the DNMT2 family, but the extent and function of 5-methyl-cytosine in the genome is unclear. Here we present the whole genome DNA methylation profile of Dictyostelium discoideum using deep coverage, replicate sequencing of bisulfite converted gDNA extracted from post-starvation cells. We find an overall very low level of DNA methylation, occurring at only 462 out of the ~7.5 million (0.006%) cytosines in the genome. Despite this sparse profile, significant methylation can be detected at 51 of these sites in replicate experiments, suggesting they are robust targets for DNA methylation. These 5-methyl-cytosines are associated with a broad range of protein-coding genes, tRNA-encoding genes and retrotransposable elements. Our data provides evidence of a minimal, but functional, methylome in Dictyostelium, thereby making Dictyostelium a candidate model organism to further investigate the evolutionary function of DNA methylation.

Non-canonical functions of the DNA methylome in gene regulation

2013 ◽  
Vol 451 (1) ◽  
pp. 13-23 ◽  
Author(s):  
James P. Reddington ◽  
Sari Pennings ◽  
Richard R. Meehan
Keyword(s):  
Dna Methylation ◽  
Gene Regulation ◽  
Transcriptional Regulation ◽  
Polycomb Group ◽  
Epigenetic Mark ◽  
Regulation Of Transcription ◽  
Gene Promoters ◽  
Dna Modification ◽  
Dna Methylome ◽  
Genomic Regions

Methylation of the cytosine base in DNA, DNA methylation, is an essential epigenetic mark in mammals that contributes to the regulation of transcription. Several advances have been made in this area in recent years, leading to a leap forward in our understanding of how this pathway contributes to gene regulation during embryonic development, and the functional consequences of its perturbation in human disease. Critical to these advances is a comprehension of the genomic distribution of modified cytosine bases in unprecedented detail, drawing attention to genomic regions beyond gene promoters. In addition, we have a more complete understanding of the multifactorial manner by which DNA methylation influences gene regulation at the molecular level, and which genes rely directly on the DNA methylome for their normal transcriptional regulation. It is becoming apparent that a major role of DNA modification is to act as a relatively stable, and mitotically heritable, template that contributes to the establishment and maintenance of chromatin states. In this regard, interplay is emerging between DNA methylation and the PcG (Polycomb group) proteins, which act as evolutionarily conserved mediators of cell identity. In the present paper we review these aspects of DNA methylation, and discuss how a multifunctional view of DNA modification as an integral part of chromatin organization is influencing our understanding of this epigenetic mark's contribution to transcriptional regulation.

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 A comparative analysis of computational tools for the prediction of epigenetic DNA methylation from long-read sequencing data

2021 ◽  
Author(s):  
Shruta Sandesh Pai ◽  
Aimee Rachel Mathew ◽  
Roy Anindya
Keyword(s):  
Dna Methylation ◽  
Dna Modification ◽  
Nanopore Sequencing ◽  
Sequencing Data ◽  
Computational Tools ◽  
Specific Location ◽  
Oxford Nanopore ◽  
Long Read ◽  
Dna Methylations ◽  
Higher Eukaryotes

AbstractRecent development of Oxford Nanopore long-read sequencing has opened new avenues of identifying epigenetic DNA methylation. Among the different epigenetic DNA methylations, N6-methyladenosine is the most prevalent DNA modification in prokaryotes and 5-methylcytosine is common in higher eukaryotes. Here we investigated if N6-methyladenosine and 5-methylcytosine modifications could be predicted from the nanopore sequencing data. Using publicly available genome sequencing data of Saccharomyces cerevisiae, we compared the open-access computational tools, including Tombo, mCaller, Nanopolish and DeepSignal for predicting 6mA and 5mC. Our results suggest that Tombo and mCaller can predict DNA N6-methyladenosine modifications at a specific location, whereas, Tombo dampened fraction, Nanopolish methylation likelihood and DeepSignal methylation probability have comparable efficiency for 5-methylcytosine prediction from Oxford Nanopore sequencing data.

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 DNA co-methylation networks outline the structure and remodeling dynamics of colorectal cancer epigenome

2018 ◽  
Author(s):  
Izaskun Mallona ◽  
Susanna Aussó ◽  
Anna Díez-Villanueva ◽  
Víctor Moreno ◽  
Miguel A. Peinado
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Colon Cancer ◽  
Genome Organization ◽  
Tumor Tissue ◽  
Network Modeling ◽  
Genome Architecture ◽  
Epigenetic Mark ◽  
And Function ◽  
Unique Signature

AbstractEpigenomic plasticity is interconnected with chromatin structure and gene regulation. In tumor progression, orchestrated remodeling of genome organization accompanies the acquisition of malignant properties. DNA methylation, a key epigenetic mark extensively altered in cancer, is also linked to genome architecture and function. Based on this association, we postulate that the dissection of long-range co-methylation structure unveils cancer cell’s genome architecture remodeling.We applied network-modeling of DNA methylation co-variation in two colon cancer cohorts and found abundant and consistent transchromosomal structures in both normal and tumor tissue. Normal-tumor comparison indicated substantial remodeling of the epigenome covariation and revealed novel genomic compartments with a unique signature of DNA methylation rank inversion.

scholarly journals Evolutionary analysis of DNA methyltransferases in microeukaryotes: Insights from the model diatom Phaeodactylum tricornutum

2021 ◽  
Author(s):  
ANTOINE HOGUIN ◽  
Ouardia Ait Mohamed ◽  
Chris Bowler ◽  
Auguste Genovesio ◽  
Fabio RJ Vieira ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Transposable Elements ◽  
Phaeodactylum Tricornutum ◽  
Dna Methyltransferase ◽  
Transcriptional Control ◽  
Dna Methyltransferases ◽  
Epigenetic Mark ◽  
Evolutionary Analysis ◽  
And Function ◽  
Dnmt Family

Cytosine DNA methylation is an important epigenetic mark in eukaryotes that is involved in the transcriptional control of mainly transposable elements in mammals, plants, and fungi. Eukaryotes encode a diverse set of DNA methyltransferases that were iteratively acquired and lost during evolution. The Stramenopiles-Alveolate-Rhizaria (SAR) lineages are a major group of ecologically important marine microeukaryotes that include the main phytoplankton classes such as diatoms and dinoflagellates. However, little is known about the diversity of DNA methyltransferases and their role in the deposition and maintenance of DNA methylation in microalgae. We performed a phylogenetic analysis of DNA methyltransferase families found in marine microeukaryotes and show that they encode divergent DNMT3, DNMT4, DNMT5 and DNMT6 enzymes family revisiting previously established phylogenies. Furthermore, we reveal a novel group of DNMTs with three classes of enzymes within the DNMT5 family. Using a CRISPR/Cas9 strategy we demonstrate that the loss of the DNMT5 gene correlates with a global depletion of DNA methylation and overexpression of transposable elements in the model diatom Phaeodactylum tricornutum. The study provides a pioneering view of the structure and function of a DNMT family in the SAR supergroup.

scholarly journals B2 SINE Copies Serve as a Transposable Boundary of DNA Methylation and Histone Modifications in the Mouse

2021 ◽  
Author(s):  
Tomoko Ichiyanagi ◽  
Hirokazu Katoh ◽  
Yoshinobu Mori ◽  
Keigo Hirafuku ◽  
Beverly Ann Boyboy ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Histone Modifications ◽  
Binding Sites ◽  
Short Interspersed Elements ◽  
Sequencing Method ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Mammalian Genomes ◽  
Mouse Species ◽  
And Function ◽  
Genomic Regions

Abstract More than one million copies of short interspersed elements (SINEs), a class of retrotransposons, are present in the mammalian genomes, particularly within gene-rich genomic regions. Evidence has accumulated that ancient SINE sequences have acquired new binding sites for transcription factors (TFs) through multiple mutations following retrotransposition, and as a result have rewired the host regulatory network during the course of evolution. However, it remains unclear whether currently active SINEs contribute to the expansion of TF binding sites. To study the mobility, expression, and function of SINE copies, we first identified about 2,000 insertional polymorphisms of SINE B1 and B2 families within Mus musculus. Using a novel RNA sequencing method designated as melRNA-seq, we detected the expression of SINEs in male germ cells at both the subfamily and genomic copy levels: the vast majority of B1 RNAs originated from evolutionarily young subfamilies, whereas B2 RNAs originated from both young and old subfamilies. DNA methylation and chromatin immunoprecipitation-sequencing (ChIP-seq) analyses in liver revealed that polymorphic B2 insertions served as a boundary element inhibiting the expansion of DNA hypomethylated and histone hyperacetylated regions, and decreased the expression of neighboring genes. Moreover, genomic B2 copies were enriched at the boundary of various histone modifications, and chromatin insulator protein, CCCTC-binding factor, a well-known chromatin boundary protein, bound to >100 polymorphic and >10,000 non-polymorphic B2 insertions. These results suggest that the currently active B2 copies are mobile boundary elements that can modulate chromatin modifications and gene expression, and are likely involved in epigenomic and phenotypic diversification of the mouse species.

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