scholarly journals Integrated transcriptomics and epigenomics reveal chamber-specific and species-specific characteristics of human and mouse hearts

PLoS Biology ◽  
2021 ◽  
Vol 19 (5) ◽  
pp. e3001229
Author(s):  
Junpeng Gao ◽  
Yuxuan Zheng ◽  
Lin Li ◽  
Minjie Lu ◽  
Xiangjian Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Human Heart ◽  
Nucleosome Occupancy ◽  
Expression Profiles ◽  
Regulation Of Gene Expression ◽  
Gene Expression Profiles ◽  
Chromatin Accessibility ◽  
Gene Body Methylation ◽  
Mammalian Heart

DNA methylation, chromatin accessibility, and gene expression represent different levels information in biological process, but a comprehensive multiomics analysis of the mammalian heart is lacking. Here, we applied nucleosome occupancy and methylome sequencing, which detected DNA methylation and chromatin accessibility simultaneously, as well as RNA-seq, for multiomics analysis of the 4 chambers of adult and fetal human hearts, and adult mouse hearts. Our results showed conserved region-specific patterns in the mammalian heart at transcriptome and DNA methylation level. Adult and fetal human hearts showed distinct features in DNA methylome, chromatin accessibility, and transcriptome. Novel long noncoding RNAs were identified in the human heart, and the gene expression profiles of major cardiovascular diseases associated genes were displayed. Furthermore, cross-species comparisons revealed human-specific and mouse-specific differentially expressed genes between the atria and ventricles. We also reported the relationship among multiomics and found there was a bell-shaped relationship between gene-body methylation and expression in the human heart. In general, our study provided comprehensive spatiotemporal and evolutionary insights into the regulation of gene expression in the heart.

scholarly journals Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Katherine R. Dobbs ◽  
Paula Embury ◽  
Emmily Koech ◽  
Sidney Ogolla ◽  
Stephen Munga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Young Adults ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Innate Immune ◽  
Inflammatory Gene Expression ◽  
Cpg Sites ◽  
Age Related ◽  
Adults And Children

Abstract Background Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. Results We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. Conclusions These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.

scholarly journals Identification of Prognostic Markers in Cholangiocarcinoma Using Altered DNA Methylation and Gene Expression Profiles

2020 ◽  
Vol 11 ◽  
Author(s):  
Nitish Kumar Mishra ◽  
Meng Niu ◽  
Siddesh Southekal ◽  
Prachi Bajpai ◽  
Amr Elkholy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Prognostic Markers ◽  
Expression Profiles ◽  
Gene Expression Profiles

scholarly journals CG gene body DNA methylation changes and evolution of duplicated genes in cassava

2015 ◽  
Vol 112 (44) ◽  
pp. 13729-13734 ◽  
Author(s):  
Haifeng Wang ◽  
Getu Beyene ◽  
Jixian Zhai ◽  
Suhua Feng ◽  
Noah Fahlgren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Gene Copy ◽  
Gene Body ◽  
Duplicated Genes ◽  
Gene Body Methylation ◽  
Substantial Impact ◽  
Tropical Regions

DNA methylation is important for the regulation of gene expression and the silencing of transposons in plants. Here we present genome-wide methylation patterns at single-base pair resolution for cassava (Manihot esculenta, cultivar TME 7), a crop with a substantial impact in the agriculture of subtropical and tropical regions. On average, DNA methylation levels were higher in all three DNA sequence contexts (CG, CHG, and CHH, where H equals A, T, or C) than those of the most well-studied model plant Arabidopsis thaliana. As in other plants, DNA methylation was found both on transposons and in the transcribed regions (bodies) of many genes. Consistent with these patterns, at least one cassava gene copy of all of the known components of Arabidopsis DNA methylation pathways was identified. Methylation of LTR transposons (GYPSY and COPIA) was found to be unusually high compared with other types of transposons, suggesting that the control of the activity of these two types of transposons may be especially important. Analysis of duplicated gene pairs resulting from whole-genome duplication showed that gene body DNA methylation and gene expression levels have coevolved over short evolutionary time scales, reinforcing the positive relationship between gene body methylation and high levels of gene expression. Duplicated genes with the most divergent gene body methylation and expression patterns were found to have distinct biological functions and may have been under natural or human selection for cassava traits.

scholarly journals Global Modulation in DNA Epigenetics during Pro-Inflammatory Macrophage Activation

2019 ◽  
Author(s):  
Nikhil Jain ◽  
Tamar Shahal ◽  
Tslil Gabrieli ◽  
Noa Gilat ◽  
Dmitry Torchinsky ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Single Molecule ◽  
Transcriptional Control ◽  
Excision Repair ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Types ◽  
Inflammatory Activation ◽  
Methylation Patterns

AbstractDNA methylation patterns create distinct gene expression profiles. These patterns are maintained after cell division, thus enabling the differentiation and maintenance of multiple cell types from the same genome sequence. The advantage of this mechanism for transcriptional control is that chemical-encoding allows to rapidly establish new epigenetic patterns “on-demand” through enzymatic methylation and de-methylation of DNA. Here we show that this feature is associated with the fast response of macrophages during their pro-inflammatory activation. By using a combination of mass spectroscopy and single-molecule imaging to quantify global epigenetic changes in the genomes of primary macrophages, we followed three distinct DNA marks (methylated, hydroxymethylated and unmethylated), involved in establishing new DNA methylation patterns during pro-inflammatory activation. The observed epigenetic modulation together with gene expression data generated for the involved enzymatic machinery, may suggest that de-methylation upon LPS-activation starts with oxidation of methylated CpGs, followed by excision-repair of these oxidized bases and their replacement with unmodified cytosine.

scholarly journals Comparison of visceral adipose tissue DNA methylation and gene expression profiles in female adolescents with obesity

2019 ◽  
Author(s):  
Matthew D. Barberio ◽  
Evan P. Nadler ◽  
Samantha Sevilla ◽  
Rosemary Lu ◽  
Brennan Harmon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Akt Signaling ◽  
Adolescent Females ◽  
Akt Signaling Pathway ◽  
Visceral Adipose

AbstractBackgroundEpigenetic changes in visceral adipose tissue (VAT) with obesity and their effects on gene expression are poorly understood, especially during emergent obesity in youth. The current study tested the hypothesis that methylation and gene expression profiles of key growth factor and inflammatory pathways such as PI3K/AKT signaling are altered in VAT from obese compared to non-obese youth.MethodsVAT samples from adolescent females grouped as Lean (L; n=15; age=15±3 yrs, BMI=21.9±3.0 kg/m2) or Obese (Ob; n=15, age=16±2 yrs, BMI=45.8±9.8 kg/m2) were collected. Global methylation (n=20) and gene expression (N=30) patterns were profiled via microarray and interrogated for differences between groups by ANCOVA (p<0.05), followed by biological pathway analysis.ResultsOverlapping differences in methylation and gene expression in 317 genes were found in VAT from obese compared to lean groups. PI3K/AKT Signaling (p=1.83×10−6; 10/121 molecules in dataset/pathway) was significantly overrepresented in Ob VAT according to pathway analysis. mRNA upregulations in the PI3K/AKT Signaling Pathway genes TFAM (p=0.03; Fold change=1.8) and PPP2R5C (p=0.03, FC=2.6) were confirmed via qRT-PCR.ConclusionOur analyses show obesity-related differences in DNA methylation and gene expression in visceral adipose tissue of adolescent females. Specifically, we identified methylation site/gene expression pairs differentially regulated and mapped these differences to PI3K/AKT signaling, suggesting that PI3K/AKT signaling pathway dysfunction in obesity may be driven in part by obesity-related changes in DNA methylation.

Abstract 4436: Synergistic effects of promoter associated DNA methylation and genetic alterations to better understand oncogenic gene expression profiles

2016 ◽  
Author(s):  
Claire Olson ◽  
Fang Yin Lo ◽  
Kerry Deutsch ◽  
Sharon Austin ◽  
Kellie Howard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Synergistic Effects ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Genetic Alterations ◽  
Oncogenic Gene

scholarly journals Comparison of visceral adipose tissue DNA methylation and gene expression profiles in female adolescents with obesity

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthew D. Barberio ◽  
Evan P. Nadler ◽  
Samantha Sevilla ◽  
Rosemary Lu ◽  
Brennan Harmon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Akt Signaling ◽  
Adolescent Females ◽  
Akt Signaling Pathway ◽  
Visceral Adipose

Abstract Background Epigenetic changes in visceral adipose tissue (VAT) with obesity and their effects on gene expression are poorly understood, especially during emergent obesity in youth. The current study tested the hypothesis that methylation and gene expression profiles of key growth factor and inflammatory pathways are altered in VAT from obese compared to non-obese youth. Methods VAT samples from adolescent females grouped as Lean (L; n = 15; age = 15 ± 3 years, BMI = 21.9 ± 3.0 kg/m2) or Obese (Ob; n = 15, age = 16 ± 2 years, BMI = 45.8 ± 9.8 kg/m2) were collected. Global methylation (n = 20) and gene expression (N = 30) patterns were profiled via microarray and interrogated for differences between groups by ANCOVA (p < 0.05), followed by biological pathway analyses. Results Overlapping differences in methylation and gene expression in 317 genes were found in VAT from obese compared to lean groups. PI3K/AKT Signaling (p = 1.83 × 10−6; 11/121 molecules in dataset/pathway) was significantly overrepresented in Ob VAT according to pathway analysis. Upregulations in the PI3K/AKT signaling pathway mRNAs TFAM (p = 0.03; fold change = 1.8) and PPP2R5C (p = 0.03, FC = 2.6) were confirmed via qRT-PCR. Conclusion Our analyses show obesity-related differences in DNA methylation and gene expression in visceral adipose tissue of adolescent females. Specifically, we identified methylation site/gene expression pairs differentially regulated and mapped these differences to pathways including PI3K/AKT signaling, suggesting that PI3K/AKT signaling pathway dysfunction in obesity may be driven in part by changes in DNA methylation.

Epigenetic tête-à-tête: the bilateral relationship between chromatin modifications and DNA methylationThis paper is one of a selection of papers published in this Special Issue, entitled 27th International West Coast Chromatin and Chromosome Conference, and has undergone the Journal's usual peer review process.

2006 ◽  
Vol 84 (4) ◽  
pp. 463-466 ◽  
Author(s):  
Ana C. D’Alessio ◽  
Moshe Szyf
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
De Novo ◽  
Peer Review Process ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cellular Transformation ◽  
Genetic Alterations ◽  
Covalent Modification ◽  
Associated Proteins

The epigenome, which comprises chromatin, associated proteins, and the pattern of covalent modification of DNA by methylation, sets up and maintains gene expression programs. It was originally believed that DNA methylation was the dominant reaction in determining the chromatin structure. However, emerging data suggest that chromatin can affect DNA methylation in both directions, triggering either de novo DNA methylation or demethylation. These events are particularly important for the understanding of cellular transformation, which requires a coordinated change in gene expression profiles. While genetic alterations can explain some of the changes, the important role of epigenetic reprogramming is becoming more and more evident. Cancer cells exhibit a paradoxical coexistence of global loss of DNA methylation with regional hypermethylation.

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