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.

scholarly journals CTCF and cohesin promote focal detachment of DNA from the nuclear lamina

2021 ◽  
Author(s):  
Tom van Schaik ◽  
Ning Qing Liu ◽  
Stefano G. Manzo ◽  
Daan Peric-Hupkes ◽  
Elzo de Wit ◽  
...  
Keyword(s):  
Stem Cells ◽  
Histone Modifications ◽  
Binding Sites ◽  
Embryonic Stem ◽  
Nuclear Lamina ◽  
Fine Tuning ◽  
Ctcf Binding ◽  
Strongly Correlated ◽  
Sharp Transition ◽  
Genomic Regions

Lamina associated domains (LADs) are large genomic regions that are positioned at the nuclear lamina (NL). It has remained largely unclear what drives the positioning and demarcation of LADs. Because the insulator protein CTCF is enriched at LAD borders, it was postulated that CTCF binding could position a subset of LAD boundaries, possibly through its function in stalling cohesin and hence preventing cohesin to invade into the LAD. To test this, we mapped genome - NL interactions in mouse embryonic stem cells after rapid depletion of CTCF and other perturbations of cohesin dynamics. CTCF and cohesin contribute to a sharp transition in NL interactions at LAD borders, whilst LADs are maintained after depletion of these proteins, also at borders marked by CTCF. CTCF and cohesin may thus reinforce LAD borders, but do not position these. CTCF binding sites within LADs are locally detached from the NL and enriched for accessible DNA and active histone modifications. Remarkably, even though NL positioning is strongly correlated with genome inactivity, this DNA remains accessible after the local detachment is lost following CTCF depletion. At a chromosomal scale, cohesin depletion and cohesin stabilization (depletion of the unloading factor WAPL) quantitatively affect NL interactions, indicative of perturbed chromosomal positioning in the nucleus. Finally, while H3K27me3 is locally enriched at CTCF-marked LAD borders, we find no evidence for an interplay between CTCF and H3K27me3 on NL interactions. Combined, these findings illustrate that CTCF and cohesin do not shape LAD patterns. Rather, these proteins mediate fine-tuning of NL interactions.

scholarly journals Gut Microbiota as Important Mediator Between Diet and DNA Methylation and Histone Modifications in the Host

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 597 ◽  
Author(s):  
Patrizia D’Aquila ◽  
Laurie Lynn Carelli ◽  
Francesco De Rango ◽  
Giuseppe Passarino ◽  
Dina Bellizzi
Keyword(s):  
Dna Methylation ◽  
Gut Microbiota ◽  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Current Evidence ◽  
Long Term Effects ◽  
Metabolic Functions ◽  
Complex Ecosystem ◽  
Short And Long Term ◽  
And Function

The human gut microbiota is a complex ecosystem consisting of trillions of microorganisms that inhabit symbiotically on and in the human intestine. They carry out, through the production of a series of metabolites, many important metabolic functions that complement the activity of mammalian enzymes and play an essential role in host digestion. Interindividual variability of microbiota structure, and consequently of the expression of its genes (microbiome), was largely ascribed to the nutritional regime. Diet influences microbiota composition and function with short- and long-term effects. In spite of the vast literature, molecular mechanisms underlying these effects still remain elusive. In this review, we summarized the current evidence on the role exerted by gut microbiota and, more specifically, by its metabolites in the establishment of the host epigenome. The interest in this topic stems from the fact that, by modulating DNA methylation and histone modifications, the gut microbiota does affect the cell activities of the hosting organism.

scholarly journals Modern approaches for investigating epigenetic signaling pathways

2010 ◽  
Vol 109 (3) ◽  
pp. 927-933 ◽  
Author(s):  
Adam G. Evertts ◽  
Barry M. Zee ◽  
Benjamin A. Garcia
Keyword(s):  
Dna Methylation ◽  
Histone Modifications ◽  
Posttranslational Modifications ◽  
Transcriptional Activation ◽  
Central Component ◽  
Experimental Conditions ◽  
Physiological Processes ◽  
Short And Long Term ◽  
Genomic Regions

Epigenetics is increasingly being recognized as a central component of physiological processes as diverse as obesity and circadian rhythms. Primarily acting through DNA methylation and histone posttranslational modifications, epigenetic pathways enable both short- and long-term transcriptional activation and silencing, independently of the underlying genetic sequence. To more quantitatively study the molecular basis of epigenetic regulation in physiological processes, the present review informs the latest techniques to identify and compare novel DNA methylation marks and combinatorial histone modifications across different experimental conditions, and to localize both DNA methylation and histone modifications over specific genomic regions.

scholarly journals Diverse roles of MeCP2 in the specification and maintenance of midbrain dopamine phenotype.

2021 ◽  
Author(s):  
Xi-Biao He ◽  
Fang Guo
Keyword(s):  
Dna Methylation ◽  
Tyrosine Hydroxylase ◽  
Dna Binding ◽  
Psychiatric Disorders ◽  
Binding Sites ◽  
Neuronal Phenotype ◽  
Midbrain Dopamine ◽  
And Function ◽  
Determining Factor

Midbrain dopamine (DA) neurons are associated with locomotor and psychiatric disorders. DA neuronal phenotype is specified in ancestral progenitors and maintained throughout differentiation. Here we demonstrate that premature MeCP2 expression prevents DA progenitors from acquiring DA phenotype through interfering NURR1 transactivation. By contrast, the maintenance of DA phenotype is not affected by MeCP2 overexpression in DA neurons. By analyzing the DNA methylation and MeCP2 binding to the promoter of DA phenotype gene tyrosine hydroxylase (Th) along differentiation, we show that Th expression is determined by TET1-mediated de-methylation of NURR1 binding sites within Th promoter. Premature MeCP2 dominates the DNA binding of these sites thereby blocking TET1 function in DA progenitors, whereas TET1 prevents excessive MeCP2 binding in DA neurons. Finally, we show that targeted de-methylation in DA progenitors protects phenotype specification from premature MeCP2 expression, whereas targeted methylation disturbs phenotype maintenance in MeCP2-overexpressed DA neurons. These findings demonstrate MeCP2 as a novel determining factor for DA neuronal phenotype and function.

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 Multiplexed single-cell profiling of chromatin states at genomic loci by expansion microscopy

2020 ◽  
Author(s):  
Marcus A. Woodworth ◽  
Kenneth K.H. Ng ◽  
Aaron R. Halpern ◽  
Nicholas A. Pease ◽  
Phuc H.B. Nguyen ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Polymerase Ii ◽  
Histone Modifications ◽  
Single Cells ◽  
Housekeeping Gene ◽  
Developmentally Regulated ◽  
Chromatin States ◽  
Histone H3k4 ◽  
And Function ◽  
Genomic Regions

AbstractProper regulation of genome architecture and activity is essential for the development and function of multicellular organisms. Histone modifications, acting in combination, specify these activity states at individual genomic loci. However, the methods used to study these modifications often require either a large number of cells or are limited to targeting one histone mark at a time. Here, we developed a new method called Single Cell Evaluation of Post-TRanslational Epigenetic Encoding (SCEPTRE) that uses Expansion Microscopy (ExM) to visualize and quantify multiple histone modifications at non-repetitive genomic regions in single cells at a spatial resolution of ~75 nm. Using SCEPTRE, we distinguished multiple histone modifications at a single housekeeping gene, quantified histone modification levels at multiple developmentally-regulated genes in individual cells, and identified a relationship between histone H3K4 trimethylation and the loading of paused RNA polymerase II at individual loci. Thus, SCEPTRE enables multiplexed detection of combinatorial chromatin states at single genomic loci in single cells.

scholarly journals Out of sight, out of mind? Germ cells and the potential impacts of epigenomic drugs

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1967 ◽  
Author(s):  
Ellen G. Jarred ◽  
Heidi Bildsoe ◽  
Patrick S. Western
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Histone Modifications ◽  
Germ Cells ◽  
Epigenetic Modifications ◽  
Reproductive Age ◽  
Specific Gene ◽  
And Function ◽  
Substantial Interest ◽  
Target Effects

Epigenetic modifications, including DNA methylation and histone modifications, determine the way DNA is packaged within the nucleus and regulate cell-specific gene expression. The heritability of these modifications provides a memory of cell identity and function. Common dysregulation of epigenetic modifications in cancer has driven substantial interest in the development of epigenetic modifying drugs. Although these drugs have the potential to be highly beneficial for patients, they act systemically and may have “off-target” effects in other cells such as the patients’ sperm or eggs. This review discusses the potential for epigenomic drugs to impact on the germline epigenome and subsequent offspring and aims to foster further examination into the possible effects of these drugs on gametes. Ultimately, the information gained by further research may improve the clinical guidelines for the use of such drugs in patients of reproductive age.

scholarly journals Molecular Processes Connecting DNA Methylation Patterns with DNA Methyltransferases and Histone Modifications in Mammalian Genomes

Genes ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 388
Author(s):  
Albert Jeltsch ◽  
Julian Broche ◽  
Pavel Bashtrykov
Keyword(s):  
Dna Methylation ◽  
Histone Modifications ◽  
Dna Methyltransferases ◽  
Molecular Processes ◽  
Mammalian Genomes ◽  
Methylation Patterns

The authors wish to make the following correction to their paper [...]

scholarly journals GoPeaks: Histone Modification Peak Calling for CUT&Tag

2022 ◽  
Author(s):  
William M Yashar ◽  
Garth Kong ◽  
Jake VanCampen ◽  
Brittany M Smith ◽  
Daniel J Coleman ◽  
...  
Keyword(s):  
Histone Modification ◽  
Histone Modifications ◽  
Chromatin Immunoprecipitation ◽  
Binomial Distribution ◽  
Read Count ◽  
Peak Calling ◽  
Genome Wide ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Genomic Regions ◽  
Covalent Histone Modifications

Genome-wide mapping of the histone modification landscape is critical to understanding tran-scriptional regulation. Cleavage Under Targets and Tagmentation (CUT&Tag) is a new method for profiling the localization of covalent histone modifications, offering improved sensitivity and decreased cost compared with Chromatin Immunoprecipitation Sequencing (ChIP-seq). Here, we present GoPeaks, a peak calling method specifically designed for histone modification CUT&Tag data. GoPeaks implements a Binomial distribution and stringent read count cut-off to nominate candidate genomic regions. We compared the performance of GoPeaks against com-monly used peak calling algorithms to detect H3K4me3, H3K4me1, and H3K27Ac peaks from CUT&Tag data. These histone modifications display a range of peak profiles and are frequently used in epigenetic studies. We found GoPeaks robustly detects genome-wide histone modifica-tions and, notably, identifies H3K27Ac with improved sensitivity compared to other standard peak calling algorithms.

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