Genomic Features: Content Sensors, Nucleotide Skew Plot, Strand Asymmetry, and DNA Methylation

AbstractBisulfite sequencing is widely used to detect 5mC and 5hmC at single base resolution. However, bisulfite treatment damages DNA resulting in fragmentation, loss of DNA and biased sequencing data. To overcome this, we developed Enzymatic Methyl-seq (EM-seq), an enzymatic based approach that uses as little as 100 pg of DNA. EM-seq outperformed bisulfite converted libraries in all metrics examined including coverage, duplication, sensitivity and nucleotide composition. EM-seq libraries displayed even GC distribution, improved correlation across input amounts as well as increased representation of genomic features. These data indicate that EM-seq is more accurate and reliable than whole genome bisulfite sequencing (WGBS).

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scMET: Bayesian modelling of DNA methylation heterogeneity at single-cell resolution

10.1101/2020.07.10.196816 ◽

2020 ◽

Author(s):

Chantriolnt-Andreas Kapourani ◽

Ricard Argelaguet ◽

Guido Sanguinetti ◽

Catalina A. Vallejos

Keyword(s):

Dna Methylation ◽

Single Cell ◽

Large Scale ◽

Regulation Of Gene Expression ◽

R Package ◽

Genomic Features ◽

Distinct Cell ◽

Selection Approach ◽

Feature Selection Approach ◽

Differential Variability

AbstractHigh throughput measurements of DNA methylomes at single-cell resolution are a promising resource to quantify the heterogeneity of DNA methylation and uncover its role in gene regulation. However, limitations of the technology result in sparse CpG coverage, effectively posing challenges to robustly quantify genuine DNA methylation heterogeneity. Here we tackle these issues by introducing scMET, a hierarchical Bayesian model which overcomes data sparsity by sharing information across cells and genomic features, resulting in a robust and biologically interpretable quantification of variability. scMET can be used to both identify highly variable features that drive epigenetic heterogeneity and perform differential methylation and differential variability analysis between pre-specified groups of cells. We demonstrate scMET’s effectiveness on some recent large scale single cell methylation datasets, showing that the scMET feature selection approach facilitates the characterisation of epigenetically distinct cell populations. Moreover, we illustrate how scMET variability estimates enable the formulation of novel biological hypotheses on the epigenetic regulation of gene expression in early development. An R package implementation of scMET is publicly available at https://github.com/andreaskapou/scMET.

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Review Selectional versus mutational mechanism underlying genomic features of bacterial strand asymmetry: a case study in Clostridium acetobutylicum

Genetics and Molecular Research ◽

10.4238/2015.march.20.1 ◽

2015 ◽

Vol 14 (1) ◽

pp. 1911-1925

Author(s):

H.-L. Zhao ◽

Z.-K. Xia ◽

Z.-G. Hua ◽

W. Wei

Keyword(s):

Clostridium Acetobutylicum ◽

Genomic Features ◽

Strand Asymmetry

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Abundant expression of maternal siRNAs is a conserved feature of seed development

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2001332117 ◽

2020 ◽

Vol 117 (26) ◽

pp. 15305-15315 ◽

Cited By ~ 3

Author(s):

Jeffrey W. Grover ◽

Diane Burgess ◽

Timmy Kendall ◽

Abdul Baten ◽

Suresh Pokhrel ◽

...

Keyword(s):

Dna Methylation ◽

Seed Development ◽

Small Rnas ◽

Sequence Evolution ◽

Small Interfering Rnas ◽

Genomic Features ◽

Pol Iv ◽

Sirna Expression ◽

Rapid Sequence ◽

And Function

Small RNAs are abundant in plant reproductive tissues, especially 24-nucleotide (nt) small interfering RNAs (siRNAs). Most 24-nt siRNAs are dependent on RNA Pol IV and RNA-DEPENDENT RNA POLYMERASE 2 (RDR2) and establish DNA methylation at thousands of genomic loci in a process called RNA-directed DNA methylation (RdDM). InBrassica rapa, RdDM is required in the maternal sporophyte for successful seed development. Here, we demonstrate that a small number of siRNA loci account for over 90% of siRNA expression duringB. rapaseed development. These loci exhibit unique characteristics with regard to their copy number and association with genomic features, but they resemble canonical 24-nt siRNA loci in their dependence on RNA Pol IV/RDR2 and role in RdDM. These loci are expressed in ovules before fertilization and in the seed coat, embryo, and endosperm following fertilization. We observed a similar pattern of 24-nt siRNA expression in diverse angiosperms despite rapid sequence evolution at siren loci. In the endosperm, siren siRNAs show a marked maternal bias, and siren expression in maternal sporophytic tissues is required for siren siRNA accumulation. Together, these results demonstrate that seed development occurs under the influence of abundant maternal siRNAs that might be transported to, and function in, filial tissues.

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Integrated analysis of the methylome and transcriptome of twin almonds (Prunus dulcis [Mill.] D.A.Webb) reveals genomic features associated with non-infectious bud failure

10.1101/2021.02.08.430330 ◽

2021 ◽

Author(s):

Katherine M. D’Amico-Willman ◽

Chad E. Niederhuth ◽

Matthew R. Willman ◽

Thomas M. Gradziel ◽

Wilburforce Z. Ouma ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Monozygotic Twin ◽

Prunus Dulcis ◽

Integrated Analysis ◽

Related Disorder ◽

Genomic Features ◽

Genetic Components ◽

Age Related ◽

Genome Wide

I.SummaryAlmond (Prunus dulcis [Mill.] D.A.Webb) exhibits an age-related disorder called non-infectious bud-failure (BF) affecting vegetative bud development and nut yield. The underlying cause of BF remains unknown but is hypothesized to be associated with heritable epigenetic mechanisms. To address this disorder and its epigenetic components, we utilized a monozygotic twin study model profiling genome-wide DNA methylation and gene expression in two sets of twin almonds discordant for BF-exhibition. Analysis of DNA methylation patterns show that BF-exhibition and methylation, namely hypomethylation, are not independent phenomena. Transcriptomic data generated from the twin pairs also shows genome-wide differential gene expression associated with BF-exhibition. After identifying differentially methylated regions (DMRs) in each twin pair, a comparison revealed 170 shared DMRs between the two twin pairs. These DMRs and the associated genetic components may play a role in BF-exhibition. A subset of 52 shared DMRs are in close proximity to genes involved in meristem maintenance, cell cycle regulation, and response to heat stress. Annotation of specific genes included involvement in processes like cell wall development, calcium ion signaling, and DNA methylation. Results of this work support the hypothesis that BF-exhibition is associated with hypomethylation in almond, and identified DMRs and differentially expressed genes can serve as potential biomarkers to assess BF-potential in almond germplasm. Our results contribute to an understanding of the contribution of epigenetic disorders in agricultural performance and biological fitness of perennials.II.SignificanceThis study examines epigenetic components underlying noninfectious bud failure, an aging-related disorder affecting almond. Results from this work contribute to our understanding of the implications of DNA methylation on agricultural production, namely perennial fruit and nut production, due to effects on growth, development, and reproduction. Describing the methylome of discordant, monozygotic twin almonds enables the study of genomic features underlying noninfectious bud failure in this economically important crop.

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Abundant expression of maternal siRNAs is a conserved feature of seed development

10.1101/866806 ◽

2019 ◽

Author(s):

Jeffrey W. Grover ◽

Diane Burgess ◽

Timmy Kendall ◽

Abdul Baten ◽

Suresh Pokhrel ◽

...

Keyword(s):

Dna Methylation ◽

Seed Development ◽

Small Rnas ◽

Copy Number ◽

Sequence Evolution ◽

Genomic Features ◽

Pol Iv ◽

Sirna Expression ◽

Rapid Sequence ◽

And Function

AbstractSmall RNAs are abundant in plant reproductive tissues, especially 24-nt short interfering (si)RNAs. Most 24-nt siRNAs are dependent on RNA Pol IV and RDR2, and establish DNA methylation at thousands of genomic loci in a process called RNA-directed DNA methylation (RdDM). In Brassica rapa, RdDM is required in the maternal sporophyte for successful seed development. Here we demonstrate that a small number of siRNA loci account for over 90% of siRNA expression during B. rapa seed development. These loci exhibit unique characteristics with regard to their copy number and association with genomic features, but they resemble canonical 24-nt siRNA loci in their dependence on RNA Pol IV/RDR2 and role in RdDM. These loci are expressed in ovules before fertilization and in the seed coat, embryo, and endosperm following fertilization. We observed a similar pattern of 24-nt siRNA expression in diverse angiosperms despite rapid sequence evolution at siren loci. In the endosperm, siren siRNAs show a marked maternal bias, and siren expression in maternal sporophytic tissues is required for siren siRNA accumulation. Together these results demonstrate that seed development occurs under the influence of abundant maternal siRNAs that might be transported to, and function in, filial tissues.Abstract Figure

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DNA methylation in satellite repeats disorders

Essays in Biochemistry ◽

10.1042/ebc20190028 ◽

2019 ◽

Vol 63 (6) ◽

pp. 757-771 ◽

Cited By ~ 4

Author(s):

Claire Francastel ◽

Frédérique Magdinier

Keyword(s):

Dna Methylation ◽

Human Genome ◽

Repetitive Dna ◽

Dna Sequences ◽

Satellite Repeats ◽

Tremendous Progress ◽

Genes Encoding ◽

Dna Elements ◽

Near Future

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.

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