scholarly journals The contrasting response to drought and waterlogging is underpinned by divergent DNA methylation programs associated with gene expression in sesame

2018 ◽  
Author(s):  
Komivi Dossa ◽  
Marie Ali Mmadi ◽  
Rong Zhou ◽  
Qi Zhou ◽  
Mei Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Abiotic Stresses ◽  
Cytosine Methylation ◽  
De Novo ◽  
Recovery Phase ◽  
Epigenetic Mechanism ◽  
Drought Tolerant ◽  
Sesame Genotypes ◽  
Methylation Patterns

AbstractDNA methylation is a heritable epigenetic mechanism that participates in gene regulation under abiotic stresses in plants. Sesame (Sesamum indicum L.) is typically considered a drought-tolerant crop but highly susceptible to waterlogging, a property attributed to its presumed origin in Africa or India. Understanding DNA methylation patterns in sesame under drought and waterlogging conditions can provide insights into the regulatory mechanisms underlying its contrasting responses to these principal abiotic stresses. Here, we combined Methylation-Sensitive Amplified Polymorphism and transcriptome analyses to profile cytosine methylation patterns, gene expression alteration, and their interplay in drought-tolerant and waterlogging-tolerant sesame genotypes under control, stress and recovery conditions. Our data showed that drought stress strongly induced de novo methylation (DNM) whereas most of the loci were demethylated (DM) during the recovery phase. In contrast, waterlogging decreased the level of methylation under stress but during the recovery phase, both DM and DNM were concomitantly deployed. In both stresses, the differentially expressed genes (DEGs) were highly correlated with the methylation patterns. We observed that DM was associated with the up-regulation of the DEGs while DNM was correlated with the down-regulation of the DEGs. In addition, we sequenced 44 differentially methylated regions of which 90% overlapped with the promoters and coding sequences of the DEGs. Altogether, we demonstrated that sesame has divergent epigenetic programs that respond to drought and waterlogging stresses. Our results also highlighted the possible interplay among DNA methylation and gene expression, which may modulate the contrasting responses to drought and waterlogging in sesame.

scholarly journals Structural insights into CpG-specific DNA methylation by human DNA methyltransferase 3B

2020 ◽  
Vol 48 (7) ◽  
pp. 3949-3961 ◽  
Author(s):  
Chien-Chu Lin ◽  
Yi-Ping Chen ◽  
Wei-Zen Yang ◽  
James C K Shen ◽  
Hanna S Yuan
Keyword(s):  
Dna Methylation ◽  
Dna Methyltransferase ◽  
Cytosine Methylation ◽  
Catalytic Domain ◽  
De Novo ◽  
Water Channel ◽  
Dna Methyltransferases ◽  
Structural Basis ◽  
Cpg Sites ◽  
Methylation Patterns

Abstract DNA methyltransferases are primary enzymes for cytosine methylation at CpG sites of epigenetic gene regulation in mammals. De novo methyltransferases DNMT3A and DNMT3B create DNA methylation patterns during development, but how they differentially implement genomic DNA methylation patterns is poorly understood. Here, we report crystal structures of the catalytic domain of human DNMT3B–3L complex, noncovalently bound with and without DNA of different sequences. Human DNMT3B uses two flexible loops to enclose DNA and employs its catalytic loop to flip out the cytosine base. As opposed to DNMT3A, DNMT3B specifically recognizes DNA with CpGpG sites via residues Asn779 and Lys777 in its more stable and well-ordered target recognition domain loop to facilitate processive methylation of tandemly repeated CpG sites. We also identify a proton wire water channel for the final deprotonation step, revealing the complete working mechanism for cytosine methylation by DNMT3B and providing the structural basis for DNMT3B mutation-induced hypomethylation in immunodeficiency, centromere instability and facial anomalies syndrome.

scholarly journals Nurse cell-derived small RNAs define paternal epigenetic inheritance in Arabidopsis

2021 ◽  
Author(s):  
Jincheng Long ◽  
James Walker ◽  
Wenjing She ◽  
Billy Aldridge ◽  
Hongbo Gao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Small Rnas ◽  
Nurse Cell ◽  
De Novo ◽  
Epigenetic Inheritance ◽  
Genome Integrity ◽  
Nurse Cells ◽  
Male Germline ◽  
Methylation Patterns

AbstractThe plant male germline undergoes DNA methylation reprogramming, which methylates genes de novo and thereby alters gene expression and facilitates meiosis. Why reprogramming is limited to the germline and how specific genes are chosen is unknown. Here, we demonstrate that genic methylation in the male germline, from meiocytes to sperm, is established by germline-specific siRNAs transcribed from transposons with imperfect sequence homology. These siRNAs are synthesized by meiocyte nurse cells (tapetum) via activity of the tapetum-specific chromatin remodeler CLASSY3. Remarkably, tapetal siRNAs govern germline methylation throughout the genome, including the inherited methylation patterns in sperm. Finally, we demonstrate that these nurse cell-derived siRNAs (niRNAs) silence germline transposons, thereby safeguarding genome integrity. Our results reveal that tapetal niRNAs are sufficient to reconstitute germline methylation patterns and drive extensive, functional methylation reprogramming analogous to piRNA-mediated reprogramming in animal germlines.

scholarly journals Silencing of Mutator Elements in Maize Involves Distinct Populations of Small RNAs and Distinct Patterns of DNA Methylation

Genetics ◽  
2020 ◽  
Vol 215 (2) ◽  
pp. 379-391 ◽  
Author(s):  
Diane Burgess ◽  
Hong Li ◽  
Meixia Zhao ◽  
Sang Yeol Kim ◽  
Damon Lisch
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Small Rnas ◽  
Cytosine Methylation ◽  
De Novo ◽  
Epigenetic Silencing ◽  
Inverted Repeats ◽  
Causal Relationships ◽  
Terminal Inverted Repeats ◽  
Silencing Pathways

Transposable elements (TEs) are a ubiquitous feature of plant genomes. Because of the threat they post to genome integrity, most TEs are epigenetically silenced. However, even closely related plant species often have dramatically different populations of TEs, suggesting periodic rounds of activity and silencing. Here, we show that the process of de novo methylation of an active element in maize involves two distinct pathways, one of which is directly implicated in causing epigenetic silencing and one of which is the result of that silencing. Epigenetic changes involve changes in gene expression that can be heritably transmitted to daughter cells in the absence of changes in DNA sequence. Epigenetics has been implicated in phenomena as diverse as development, stress response, and carcinogenesis. A significant challenge facing those interested in investigating epigenetic phenomena is determining causal relationships between DNA methylation, specific classes of small RNAs, and associated changes in gene expression. Because they are the primary targets of epigenetic silencing in plants and, when active, are often targeted for de novo silencing, TEs represent a valuable source of information about these relationships. We use a naturally occurring system in which a single TE can be heritably silenced by a single derivative of that TE. By using this system it is possible to unravel causal relationships between different size classes of small RNAs, patterns of DNA methylation, and heritable silencing. Here, we show that the long terminal inverted repeats within Zea mays MuDR transposons are targeted by distinct classes of small RNAs during epigenetic silencing that are dependent on distinct silencing pathways, only one of which is associated with transcriptional silencing of the transposon. Further, these small RNAs target distinct regions of the terminal inverted repeats, resulting in different patterns of cytosine methylation with different functional consequences with respect to epigenetic silencing and the heritability of that silencing.

Changes in DNA methylation during mouse embryonic development in relation to X-chromosome activity and imprinting

1990 ◽  
Vol 326 (1235) ◽  
pp. 299-312 ◽  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Embryonic Development ◽  
X Chromosome ◽  
De Novo ◽  
Germ Line ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Chromatin Configuration ◽  
Methylation Patterns

Changing DNA methylation patterns during embryonic development are discussed in relation to differential gene expression, changes in X-chromosome activity and genomic imprinting. Sperm DNA is more methylated than oocyte DNA, both overall and for specific sequences. The methylation difference between the gametes could be one of the mechanisms (along with chromatin structure) regulating initial differences in expression of parental alleles in early development. There is a loss of methylation during development from the morula to the blastocyst and a marked decrease in methylase activity. De novo methylation becomes apparent around the time of implantation and occurs to a lesser extent in extra-embryonic tissue DNA. In embryonic DNA, de novo methylation begins at the time of random X-chromosome inactivation but it continues to occur after X-chromosome inactivation and may be a mechanism that irreversibly fixes specific patterns of gene expression and X-chromosome inactivity in the female. The germ line is probably delineated before extensive de novo methylation and hence escapes this process. The marked undermethylation of the germ line DNA may be a prerequisite for X-chromosome reactivation. The process underlying reactivation and removal of parent-specific patterns of gene expression may be changes in chromatin configuration associated with meiosis and a general reprogramming of the germ line to developmental totipotency.

scholarly journals Epigenetic Basis of Molecular Changes in Animal Cells with Particular Regard to Embryonic Development – A Review / Epigenetyczne Podstawy Przemian Molekularnych Zachodzących W Komórkach Zwierzęcych, Ze Szczególnym Uwzględnieniem Rozwoju Embrionalnego – Artykuł Przeglądowy

2013 ◽  
Vol 13 (4) ◽  
pp. 675-685
Author(s):  
Joanna Romanek
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Embryonic Development ◽  
De Novo ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Epigenetic Mechanism ◽  
Animal Cells ◽  
Molecular Changes ◽  
De Novo Methylation

Abstract Regulation of gene expression is a complex process. Epigenetics is the study of heritable changes in gene expression independently of DNA sequence. Epigenetic control of gene transcription is based on two main processes. The first is reversible DNA methylation, primarily of cytosine at position C5, rarely in position N3, or of adenine at position C6 (Xu et al., 2010). The second process is the change in chromatin structure and function by chemical modification of histones, including mainly methylation, acetylation, and phosphorylation of histone amino acids (Zamudio et al., 2008). During development and differentiation of cells, changes occur in DNA methylation of genes. After fertilization there are dynamic histone modifications and changes in DNA methylation in zygotes. Use of methylation sensitive restriction enzymes causes a global demethylation in the early embryonic stage (Sulewska et al., 2007 b). De novo methylation of CpG sites is followed by embryo implantation. Next, during gastrulation most genes are methylated except the tissue-specific genes. The last wave of de novo methylation takes place during the gametogenesis and is dependent on sex (Sulewska et al., 2007 b). The aim of this work is to review the current knowledge about epigenetic mechanism of molecular changes in animal cells with particular regard to embryonic development.

scholarly journals Silencing of Mu elements in maize involves distinct populations of small RNAs and distinct patterns of DNA methylation

2020 ◽  
Author(s):  
Diane Burgess ◽  
Meixia Zhao ◽  
Sang Yeol Kim ◽  
Damon Lisch
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Small Rnas ◽  
Cytosine Methylation ◽  
De Novo ◽  
Epigenetic Silencing ◽  
Causal Relationships ◽  
Daughter Cells ◽  
Functional Consequences ◽  
Silencing Pathways

Epigenetic changes involve changes in gene expression that can be heritably transmitted to daughter cells in the absence of changes in DNA sequence. Epigenetics has been implicated in phenomena as diverse as development, stress response and carcinogenesis. A significant challenge facing those interested in investigating epigenetic phenomena is determining causal relationships between DNA methylation, specific classes of small RNAs and associated changes in gene expression. Because they are the primary targets of epigenetic silencing in plants and, when active, are often targeted for de novo silencing, transposable elements (TEs) represent a valuable source of information about these relationships. We use a naturally occurring system in which a single TE can be heritably silenced by a single derivative of that TE. By using this system it is possible to unravel causal relationships between different size classes of small RNAs, patterns of DNA methylation and heritable silencing. Here, we show that the long terminal inverted repeats (TIRs) within Zea mays MuDR transposons are targeted by distinct classes of small RNAs during epigenetic silencing that are dependent on distinct silencing pathways. Further, these small RNAs target distinct regions of the TIRs, resulting in different patterns of cytosine methylation with different functional consequences with respect to epigenetic silencing and heritability of that silencing.

scholarly journals Pioneer transcription factors are associated with the modulation of DNA methylation patterns across cancers

2021 ◽  
Author(s):  
Roza Berhanu Lemma ◽  
Thomas Fleischer ◽  
Emily Martinsen ◽  
Vessela N Kristensen ◽  
Ragnhild Eskeland ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transcription Factors ◽  
Gene Expression Regulation ◽  
De Novo ◽  
Aberrant Methylation ◽  
Cancer Types ◽  
Aberrant Dna Methylation ◽  
Methylation Patterns ◽  
Mcf 7

Methylation of cytosines on DNA is a prominent modification associated with gene expression regulation. Aberrant DNA methylation patterns have recurrently been linked to dysregulation of the regulatory program in cancer cells. To shed light on the underlying molecular mechanism driving this process, we hypothesized that aberrant methylation patterns could be controlled by the binding of specific transcription factors (TFs) across cancer types. By combining DNA methylation arrays and gene expression data with TF binding sites (TFBSs), we explored the interplay between TF binding and DNA methylation in 19 cancer cohorts. We performed emQTL (expression-methylation quantitative trait loci) analyses in each cohort and identified 13 TFs whose expression levels are correlated with local DNA methylation patterns around their binding site in at least 2 cancer types. The 13 TFs are mainly associated with local demethylation and are enriched for pioneer function, suggesting a specific role for these TFs in modulating chromatin structure and transcription in cancer patients. Furthermore, we confirmed that de novo methylation is precluded across cancers at CpGs lying in genomic regions enriched for TF-binding signatures associated with SP1, CTCF, NRF1, GABPA, KLF9, and/or YY1. The modulation of DNA methylation associated with TF binding was observed at cis-regulatory regions controlling immune- and cancer-associated pathways, corroborating that the emQTL signals were derived from both cancer and tumour-infiltrating cells. As a case example, we experimentally confirmed that FOXA1 knock-down is associated with higher methylation in regions bound by FOXA1 in breast cancer MCF-7 cells. Finally, we reported physical interactions between FOXA1 with TET1 and TET2 at physiological levels in MCF-7 cells, adding further support for FOXA1 attracting TET1 and TET2 to induce local demethylation in cancer.

Directed De Novo DNA Methylation of a Genomic Locus Leads to Heritable Transcriptional Repression.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 343-343
Author(s):  
Kevin G. Ford ◽  
Paul J. Hurd ◽  
Andrew J. Bannister ◽  
Tony Kouzarides ◽  
Alexander E. Smith
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transcriptional Repression ◽  
Cytosine Methylation ◽  
De Novo ◽  
Genomic Locus ◽  
Repressive Chromatin ◽  
First Time ◽  
Dna Cytosine Methylation ◽  
De Novo Methylation

Abstract The ability to impose exogenous targeted epigenetic changes in the genome represents an attractive goal in gene therapy for the heritable repression of target genes, while potentially enabling the generation and subsequent study of the downstream effects of de novo epigenetic events, which are known to occur in disease. Here we demonstrate the ability of zinc-finger peptides to deliver DNA cytosine methylation in vivo to a genomic target promoter, when expressed as fusions with a mutant prokaryotic DNA cytosine methyltransferase enzyme, thus mimicking cellular de novo methylation events. We show for the first time targeted gene silencing in response to directed DNA cytosine methylation via initiation of a repressive chromatin signature at a targeted genomic locus, characterised by elevation of histone H3K9Me2 and reduction of H3K4Me3 levels at that region. This transcriptional repression is maintained in the absence of sustained targeted methyltransferase action, confirming epigenetic maintenance by the cells own machinery. The inherited DNA methylation pattern is restricted to specific target sites, suggesting that the establishment of repressive chromatin structure does not drive further de novo DNA methylation in this system. Therefore, we demonstrate for the first time, targeted DNA methyltransferases as potential tools for the exogenous and heritable control of gene expression at the chromosomal level, while providing the clearest and most direct confirmation to date of the functional and mechanistic consequences of de novo DNA methylation in the cell. This work represents an important step towards the longer term goal of controlling gene expression through the inheritance of a repressive DNA state, as well as providing a valuable tool for studying spatial and temporal issues associated with ‘genuine’ de novo methylation, on transcription and chromatin structure.

scholarly journals Variants ofDNMT3Acause transcript-specific DNA methylation patterns and affect hematopoietic differentiation

2018 ◽  
Author(s):  
Tanja Božić ◽  
Joana Frobel ◽  
Annamarija Raic ◽  
Fabio Ticconi ◽  
Chao-Chung Kuo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Myeloid Leukemia ◽  
Dna Methyltransferase ◽  
De Novo ◽  
Hematopoietic Differentiation ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Methylation Patterns

AbstractThede novoDNA methyltransferase 3A (DNMT3A) plays pivotal roles in hematopoietic differentiation. In this study, we followed the hypothesis that alternative splicing ofDNMT3Ahas characteristic epigenetic and functional sequels. SpecificDNMT3Atranscripts were either downregulated or overexpressed in human hematopoietic stem and progenitor cells and this resulted in complementary and transcript-specific DNA methylation and gene expression changes. Functional analysis indicated that particularly transcript 2 (coding for DNMT3A2) activates proliferation and induces loss of a primitive immunophenotype, whereas transcript 4 interferes with colony formation of the erythroid lineage. Notably, in acute myeloid leukemia (AML) expression of transcript 2 correlates with itsin vitroDNA methylation and gene expression signatures and is associated with overall survival, indicating thatDNMT3Avariants impact also on malignancies. Our results demonstrate that specificDNMT3Avariants have distinct epigenetic and functional impact. Particularly DNMT3A2 triggers hematopoietic differentiation and the corresponding signatures are reflected in AML.

scholarly journals Nurse cell­–derived small RNAs define paternal epigenetic inheritance in Arabidopsis

Science ◽  
2021 ◽  
Vol 373 (6550) ◽  
pp. eabh0556 ◽  
Author(s):  
Jincheng Long ◽  
James Walker ◽  
Wenjing She ◽  
Billy Aldridge ◽  
Hongbo Gao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Small Rnas ◽  
De Novo ◽  
Epigenetic Inheritance ◽  
Genome Integrity ◽  
Nurse Cells ◽  
Small Interfering Rnas ◽  
Male Germline ◽  
Methylation Patterns

The plant male germline undergoes DNA methylation reprogramming, which methylates genes de novo and thereby alters gene expression and regulates meiosis. Here, we reveal the molecular mechanism underlying this reprogramming. We demonstrate that genic methylation in the male germline, from meiocytes to sperm, is established by 24-nucleotide small interfering RNAs (siRNAs) transcribed from transposons with imperfect sequence homology. These siRNAs are synthesized by meiocyte nurse cells (tapetum) through activity of CLSY3, a chromatin remodeler absent in other anther cells. Tapetal siRNAs govern germline methylation throughout the genome, including the inherited methylation patterns in sperm. Tapetum-derived siRNAs also silence germline transposons, safeguarding genome integrity. Our results reveal that tapetal siRNAs are sufficient to reconstitute germline methylation patterns and drive functional methylation reprogramming throughout the male germline.

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