Maternal high-zinc diet attenuates intestinal inflammation by reducing DNA methylation and elevating H3K9 acetylation in the A20 promoter of offspring chicks

Background: Inflammatory bowel disease (IBD) is a multifactorial condition influenced by the immune system, the intestinal microbiota, environmental factors, genetic and epigenetic factors. Genetic- and environment-induced dysregulation of the Nuclear Factor-kappa B (NF-κB) transcription factor pathway has been linked to IBD pathogenesis. Objective: To assess the current evidence in relation to the contribution of the classical and alternative NF-κB pathways in IBD and to discuss the epigenetic mechanisms that impact on NF-κB function. Methods: A Medline search for ‘NF-kappaB/NF-κB’, in combination with terms including ‘inflammatory bowel disease/IBD’, 'intestinal inflammation', ‘Crohn's disease’, ‘ulcerative colitis’, 'colitis'; ‘epigenetics’, ‘DNA methylation’, ‘histones’, ‘microRNAs/miRNAs’ and ‘short non-coding/long non-coding RNAs’ was performed. Results: Both NF-κB pathways contribute to the chronic inflammation underlying IBD by regulating the inflammatory immune responses and homeostasis of the intestinal epithelium (classical pathway) or regulating bowel inflammation and epithelial microfold (M) cell function (alternative pathway). DNA methylation is a common epigenetic modification in intestinal inflammation, including NFKB1 and RELA loci. Conversely, little is understood regarding epigenetic effects on genes encoding other NF-κB subunits, particularly those of the alternative pathway, and in the context of IBD. However, NF-κB interaction with chromatin modifiers is also seen to be an essential mechanism of regulation of downstream target genes relevant to NF-κB-mediated inflammatory responses. Conclusion: Further research is clearly warranted in this area, as understanding the cell-specific regulation of the NF-κB pathways will bring researchers into a position to achieve more efficient stratification of IBD patients, and more targeted and effective choice of treatment.

Dose- and time- effect responses of DNA methylation and histone H3K9 acetylation changes induced by traffic-related air pollution

Scientific Reports ◽

10.1038/srep43737 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 21

Author(s):

Rui Ding ◽

Yongtang Jin ◽

Xinneng Liu ◽

Huaizhuang Ye ◽

Ziyi Zhu ◽

...

Keyword(s):

Dna Methylation ◽

Air Pollution ◽

Time Effect ◽

H3k9 Acetylation

Differential regulation of DNA methylation versus histone acetylation in cardiomyocytes during HHcy in vitro and in vivo: an epigenetic mechanism

Physiological Genomics ◽

10.1152/physiolgenomics.00168.2013 ◽

2014 ◽

Vol 46 (7) ◽

pp. 245-255 ◽

Cited By ~ 35

Author(s):

Pankaj Chaturvedi ◽

Anuradha Kalani ◽

Srikanth Givvimani ◽

Pradip Kumar Kamat ◽

Anastasia Familtseva ◽

...

Keyword(s):

Dna Methylation ◽

Histone Acetylation ◽

Dna Methyltransferase ◽

Epigenetic Mechanism ◽

Dependent Manner ◽

Histone Deacetylase 1 ◽

H3k9 Acetylation ◽

Dose Dependent

The mechanisms of homocysteine-mediated cardiac threats are poorly understood. Homocysteine, being the precursor to S-adenosyl methionine (a methyl donor) through methionine, is indirectly involved in methylation phenomena for DNA, RNA, and protein. We reported previously that cardiac-specific deletion of N-methyl-d-aspartate receptor-1 (NMDAR1) ameliorates homocysteine-posed cardiac threats, and in this study, we aim to explore the role of NMDAR1 in epigenetic mechanisms of heart failure, using cardiomyocytes during hyperhomocysteinemia (HHcy). High homocysteine levels activate NMDAR1, which consequently leads to abnormal DNA methylation vs. histone acetylation through modulation of DNA methyltransferase 1 (DNMT1), HDAC1, miRNAs, and MMP9 in cardiomyocytes. HL-1 cardiomyocytes cultured in Claycomb media were treated with 100 μM homocysteine in a dose-dependent manner. NMDAR1 antagonist (MK801) was added in the absence and presence of homocysteine at 10 μM in a dose-dependent manner. The expression of DNMT1, histone deacetylase 1 (HDAC1), NMDAR1, microRNA (miR)-133a, and miR-499 was assessed by real-time PCR as well as Western blotting. Methylation and acetylation levels were determined by checking 5′-methylcytosine DNA methylation and chromatin immunoprecipitation. Hyperhomocysteinemic mouse models (CBS+/−) were used to confirm the results in vivo. In HHcy, the expression of NMDAR1, DNMT1, and matrix metalloproteinase 9 increased with increase in H3K9 acetylation, while HDAC1, miR-133a, and miR-499 decreased in cardiomyocytes. Similar results were obtained in heart tissue of CBS+/− mouse. High homocysteine levels instigate cardiovascular remodeling through NMDAR1, miR-133a, miR-499, and DNMT1. A decrease in HDAC1 and an increase in H3K9 acetylation and DNA methylation are suggestive of chromatin remodeling in HHcy.

Oocyte vitrification induces loss of DNA methylation and histone acetylation in the resulting embryos derived using ICSI in dromedary camel

Zygote ◽

10.1017/s0967199421000150 ◽

2021 ◽

pp. 1-10

Author(s):

F. Moulavi ◽

I.M. Saadeldin ◽

A.A. Swelum ◽

F. Tasdighi ◽

H. Hosseini-Fahraji ◽

...

Keyword(s):

Dna Methylation ◽

Blastocyst Stage ◽

Epigenetic Reprogramming ◽

Developmental Competence ◽

Oocyte Cryopreservation ◽

Dromedary Camel ◽

Cleavage Rate ◽

Oocyte Vitrification ◽

Preimplantation Embryo Development ◽

H3k9 Acetylation

Summary Oocyte cryopreservation has become an important component of assisted reproductive technology with increasing implication in female fertility preservation and animal reproduction. However, the possible adverse effects of oocyte cryopreservation on epigenetic status of the resulting embryos is still an open question. This study evaluated the effects of MII-oocyte vitrification on gene transcripts linked to epigenetic reprogramming in association with the developmental competence and epigenetic status of the resulting embryos at 2-cell and blastocyst stages in dromedary camel. The cleavage rate of vitrified oocytes following intracytoplasmic sperm injection was significantly increased compared with the control (98.2 ± 2 vs. 72.7 ± 4.1%, respectively), possibly due to the higher susceptibility of vitrified oocytes to spontaneous activation. Nonetheless, the competence of cleaved embryos derived from vitrified oocytes for development to the blastocyst and hatched blastocyst was significantly reduced compared with the control (7.7 ± 1.2 and 11.1 ± 11.1 compared with 28.1 ± 2.6 and 52.4 ± 9.9%, respectively). The relative transcript abundances of epigenetic reprogramming genes DNMT1, DNMT3B, HDAC1, and SUV39H1 were all significantly reduced in vitrified oocytes relative to the control. Evaluation of the epigenetic marks showed significant reductions in the levels of DNA methylation (6.1 ± 0.3 vs. 9.9 ± 0.5, respectively) and H3K9 acetylation (7.8 ± 0.2 vs. 10.7 ± 0.3, respectively) in 2-cell embryos in the vitrification group relative to the control. Development to the blastocyst stage partially adjusted the effects that oocyte vitrification had on the epigenetic status of embryos (DNA methylation: 4.9 ± 0.4 vs. 6.2 ± 0.6; H3K9 acetylation: 5.8 ± 0.3 vs. 8 ± 0.9, respectively). To conclude, oocyte vitrification may interfere with the critical stages of epigenetic reprogramming during preimplantation embryo development.

Blood-Derived DNA Methylation Signatures of Crohn's Disease and Severity of Intestinal Inflammation

Gastroenterology ◽

10.1053/j.gastro.2019.01.270 ◽

2019 ◽

Vol 156 (8) ◽

pp. 2254-2265.e3 ◽

Cited By ~ 16

Author(s):

Hari K. Somineni ◽

Suresh Venkateswaran ◽

Varun Kilaru ◽

Urko M. Marigorta ◽

Angela Mo ◽

...

Keyword(s):

Dna Methylation ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Intestinal Inflammation

Glucocorticoid Programming of the Fetal Male Hippocampal Epigenome

Endocrinology ◽

10.1210/en.2012-1980 ◽

2013 ◽

Vol 154 (3) ◽

pp. 1168-1180 ◽

Cited By ~ 62

Author(s):

Ariann Crudo ◽

Matthew Suderman ◽

Vasilis G. Moisiadis ◽

Sophie Petropoulos ◽

Alisa Kostaki ◽

...

Keyword(s):

Dna Methylation ◽

Promoter Methylation ◽

Plasma Cortisol ◽

Late Gestation ◽

Gene Promoters ◽

Fetal Plasma ◽

Genome Wide ◽

Organ Systems ◽

Increased Risk ◽

H3k9 Acetylation

Abstract The late-gestation surge in fetal plasma cortisol is critical for maturation of fetal organ systems. As a result, synthetic glucocorticoids (sGCs) are administered to pregnant women at risk of delivering preterm. However, animal studies have shown that fetal exposure to sGC results in increased risk of behavioral, endocrine, and metabolic abnormalities in offspring. Here, we test the hypothesis that prenatal GC exposure resulting from the fetal cortisol surge or after sGC exposure results in promoter-specific epigenetic changes in the hippocampus. Fetal guinea pig hippocampi were collected before (gestational day [GD52]) and after (GD65) the fetal plasma cortisol surge (Term∼GD67) and 24 hours after (GD52) and 14 days after (GD65) two repeat courses of maternal sGC (betamethasone) treatment (n = 3–4/gp). We identified extensive genome-wide alterations in promoter methylation in late fetal development (coincident with the fetal cortisol surge), whereby the majority of the affected promoters exhibited hypomethylation. Fetuses exposed to sGC in late gestation exhibited substantial differences in DNA methylation and histone h3 lysine 9 (H3K9) acetylation in specific gene promoters; 24 hours after the sGC treatment, the majority of genes affected were hypomethylated or hyperacetylated. However, 14 days after sGC exposure these differences did not persist, whereas other promoters became hypermethylated or hyperacetylated. These data support the hypothesis that the fetal GC surge is responsible, in part, for significant variations in genome-wide promoter methylation and that prenatal sGC treatment profoundly changes the epigenetic landscape, affecting both DNA methylation and H3K9 acetylation. This is important given the widespread use of sGC in the management of women in preterm labor.

DNA methylation within intron 2 of the Stat1 gene is reduced in colon tissue from interleukin-10 gene-deficient mice compared with healthy control mice

10.7287/peerj.preprints.1391 ◽

2015 ◽

Author(s):

Matthew PG Barnett ◽

Anna E Russ ◽

Warren C McNabb ◽

Nicole C Roy

Keyword(s):

Dna Methylation ◽

Mouse Model ◽

Intestinal Inflammation ◽

Interleukin 10 ◽

Preliminary Evidence ◽

Proximal Promoter ◽

Colon Tissue ◽

Cpg Sites ◽

Human Inflammatory Bowel Disease ◽

Intron 2

Background. Epigenetic influences have been implicated in the development of autoimmunity. While such mechanisms have been linked to mouse models of intestinal inflammation, and to human inflammatory bowel disease (IBD), the involvement of epigenetic mechanisms in the pathogenesis of intestinal inflammation in the interleukin-10 gene-deficient (Il10 –/– ) mouse model of IBD has not yet been reported. This study investigated the hypothesis that changes observed in the expression of Stat1 and Ppara in colon tissue of Il10 –/– mice are associated with differential methylation of CpG sites within key regulatory regions of these genes. Methods. Colon tissue was collected from Il10 –/– and C57BL/6JArc mice at 6 (pre-inflammation) or 12 (established inflammation) weeks of age. Methylation levels of CpG sites within selected regions of the Stat1 and Ppara genes were assessed using MALDI-TOF mass spectrometry in DNA extracted from mouse colon tissue. Results. Methylation of specific CpG sites within intron 2, but not the proximal promoter, of the Stat1 gene was reduced in colon tissue from Il10 –/– mice at 12 weeks of age compared with colon tissue C57BL/6JArc mice at 12 weeks of age. Discussion. These data provide preliminary evidence that DNA methylation is altered in the Il10 –/– mouse model of IBD, and this may be linked with changes in the expression levels of genes that play a key role in inflammation. Further studies are required to confirm these observations, and to establish a causative link between methylation at specific sites (such as intron 2 of Stat1) and gene expression.

DNA methylation within intron 2 of the Stat1 gene is reduced in colon tissue from interleukin-10 gene-deficient mice compared with healthy control mice

10.7287/peerj.preprints.1391v1 ◽

2015 ◽

Author(s):

Matthew PG Barnett ◽

Anna E Russ ◽

Warren C McNabb ◽

Nicole C Roy

Keyword(s):

Dna Methylation ◽

Mouse Model ◽

Intestinal Inflammation ◽

Interleukin 10 ◽

Preliminary Evidence ◽

Proximal Promoter ◽

Colon Tissue ◽

Cpg Sites ◽

Human Inflammatory Bowel Disease ◽

Intron 2

Background. Epigenetic influences have been implicated in the development of autoimmunity. While such mechanisms have been linked to mouse models of intestinal inflammation, and to human inflammatory bowel disease (IBD), the involvement of epigenetic mechanisms in the pathogenesis of intestinal inflammation in the interleukin-10 gene-deficient (Il10 –/– ) mouse model of IBD has not yet been reported. This study investigated the hypothesis that changes observed in the expression of Stat1 and Ppara in colon tissue of Il10 –/– mice are associated with differential methylation of CpG sites within key regulatory regions of these genes. Methods. Colon tissue was collected from Il10 –/– and C57BL/6JArc mice at 6 (pre-inflammation) or 12 (established inflammation) weeks of age. Methylation levels of CpG sites within selected regions of the Stat1 and Ppara genes were assessed using MALDI-TOF mass spectrometry in DNA extracted from mouse colon tissue. Results. Methylation of specific CpG sites within intron 2, but not the proximal promoter, of the Stat1 gene was reduced in colon tissue from Il10 –/– mice at 12 weeks of age compared with colon tissue C57BL/6JArc mice at 12 weeks of age. Discussion. These data provide preliminary evidence that DNA methylation is altered in the Il10 –/– mouse model of IBD, and this may be linked with changes in the expression levels of genes that play a key role in inflammation. Further studies are required to confirm these observations, and to establish a causative link between methylation at specific sites (such as intron 2 of Stat1) and gene expression.

Blood-based DNA methylation in Crohn’s disease and severity of intestinal inflammation

Translational Gastroenterology and Hepatology ◽

10.21037/tgh.2019.10.03 ◽

2019 ◽

Vol 4 ◽

pp. 76-76 ◽

Cited By ~ 1

Author(s):

Rahul Kalla ◽

Alex T. Adams ◽

Jack Satsangi

Keyword(s):

Dna Methylation ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Intestinal Inflammation

Aberrant levels of DNA methylation and H3K9 acetylation in the testicular cells of crossbred cattle‐yak showing infertility

Reproduction in Domestic Animals ◽

10.1111/rda.14061 ◽

2021 ◽

Author(s):

Praopilas Phakdeedindan ◽

Manita Wittayarat ◽

Theerawat Tharasanit ◽

Mongkol Techakumphu ◽

Megumi Shimazaki ◽

...

Keyword(s):

Dna Methylation ◽

Crossbred Cattle ◽

Testicular Cells ◽

H3k9 Acetylation