A methyl‐deficient diet modifies histone methylation and alters <i>Igf2</i> and <i>H19</i> repression in the prostate

Dobosy, Joseph R.; Fu, Vivian; Desotelle, Joshua A.; Srinivasan, Rajini; Kenowski, Michelle L.; Almassi, Nima; Weindruch, Richard; Svaren, John; Jarrard, David F.

doi:10.1002/pros.20782

Cited by 69 publications

(54 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, lack of DNA methylation in the ICR of IGF2/H19 together with no detectable level of dimethyl H3K9 in PCa might provoke binding of CTCF to this region resulting in enhanced expression of H19, the role of which in carcinogenesis is still unclear. Interestingly, recent study from Dobosy et al (31) provided evidence that folateand methyl-deficient diet causes decrease in di-methyl H3K9 modification within H19 promoter in prostate tissue of mature mice which also has been observed in our ChIP assay on human PCa tissue. Further studies investigating the relationship between DNA methylation, chromatin structure and DNA accessibility will provide insights into the epigenetic regulation of the IGF2/H19 locus in PCa.…”

Section: Discussionsupporting

confidence: 82%

Aberrant epigenetic modifications in the CTCF binding domain of the IGF2/H19 gene in prostate cancer compared with benign prostate hyperplasia

Paradowska

Fenic²,

Konrad³

et al. 2009

Int J Oncol

View full text Add to dashboard Cite

Abstract. Expression of the imprinted genes insulin-like growth factor 2 (IGF2) and H19 depends on the methylation pattern of their common imprinting control region (ICR) located on chromosome 11p15. As the somatic imprinting pattern may be lost during tumorigenesis due to epigenetic alterations, in the present study, we analyzed the DNA methylation and histone modifications in the differentially methylated region (DMR) of IGF2/H19 in benign prostate hyperplasia (BPH) and prostate carcinoma (PCa). Sodium bisulfite sequencing was performed on frozen tissue collected after radical prostatectomy. Thirty tumors and 17 noncancerous tissue samples were analyzed. Histological diagnosis was, in addition, confirmed by amplification of the epithelial tumor marker ·-methylacyl coenzyme-A racemase. Chromatin immunoprecipitation assay (ChIP) was carried out on sonificated chromatin from fresh tissue samples from 10 PCa, 10 BPH using antibodies against trimethyl histone H3K9, dimethyl histone H3K9, trimethyl H3K27 and acetyl H3K9. The methylation pattern of 17 CpGs within 227 bp of the H19 fragment was characterized from each DNA sample. All (BPH) samples demonstrated >80% methylation of CpGs. In contrast, we found 41% of CpGs methylated in 9 out of 30 PCa specimens. We observed statistically significant differences in the methylation state between PCa and BPH groups, especially in the DMR of H19 (p<0.0001) and in the ICR (p=0.0034), which corresponds to CTCF binding domain. ChIP assay revealed that dimethyl H3K9 is associated with the ICR of IGF2/H19 in BPH, but not in PCa (p<0.0001). Our data demonstrate that DNA methylation and histone methylation analysis of the ICR within the DMR of IGF2/H19 provides important insights into early steps of carcinogenesis and, therefore, may contribute to improving diagnosis of PCa.

show abstract

Section: Discussionsupporting

confidence: 82%

Aberrant epigenetic modifications in the CTCF binding domain of the IGF2/H19 gene in prostate cancer compared with benign prostate hyperplasia

Paradowska

Fenic²,

Konrad³

et al. 2009

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…Hypomethylation of IGF2 P3 is responsible for upregulated IGF2 transcription and has an active role in osteosarcoma and hepatoblastoma (12,27). Several clinical studies have shown a positive correlation between plasma DHA concentration and erythrocyte folate level or serum vitamin B 6 and B 12 , reported to be methylation modulators of imprinted genes (25,47,49). Interestingly, a choline-and methionine-deficient diet revealed a decrease of repressive dimethylation at histone H3 lysine 9 (H3K9) within H19 promoter as well as Igf2 P2 and P3 (6).…”

Section: Discussionmentioning

confidence: 99%

“…Several clinical studies have shown a positive correlation between plasma DHA concentration and erythrocyte folate level or serum vitamin B 6 and B 12 , reported to be methylation modulators of imprinted genes (25,47,49). Interestingly, a choline-and methionine-deficient diet revealed a decrease of repressive dimethylation at histone H3 lysine 9 (H3K9) within H19 promoter as well as Igf2 P2 and P3 (6). We found that DHA had a much stronger effect on hypomethylation of IGF2 P3, in accordance with findings from Ba et al (1) in preterm infants, and maternal DHA supplementation has shown a preventive effect of longer gestational duration (3).…”

Section: Discussionmentioning

confidence: 99%

Dietary supplementation with polyunsaturated fatty acid during pregnancy modulates DNA methylation at IGF2/H19 imprinted genes and growth of infants

Lee

Barraza‐Villarreal

Biessy³

et al. 2014

Physiological Genomics

View full text Add to dashboard Cite

I. Dietary supplementation with polyunsaturated fatty acid during pregnancy modulates DNA methylation at IGF2/H19 imprinted genes and growth of infants. Physiol Genomics 46: 851-857, 2014. First published October 7, 2014 doi:10.1152/physiolgenomics.00061.2014.-Epigenetic regulation of imprinted genes is regarded as a highly plausible explanation for linking dietary exposures in early life with the onset of diseases during childhood and adulthood. We sought to test whether prenatal dietary supplementation with docosahexaenoic acid (DHA) during pregnancy may modulate epigenetic states at birth. This study was based on a randomized intervention trial conducted in Mexican pregnant women supplemented daily with 400 mg of DHA or a placebo from gestation week 18 -22 to parturition. We applied quantitative profiling of DNA methylation states at IGF2 promoter 3 (IGF2 P3), IGF2 differentially methylated region (DMR), and H19 DMR in cord blood mononuclear cells of the DHA-supplemented group (n ϭ 131) and the control group (n ϭ 130). In stratified analyses, DNA methylation levels in IGF2 P3 were significantly higher in the DHA group than the control group in preterm infants (P ϭ 0.04). We also observed a positive association between DNA methylation levels and maternal body mass index; IGF2 DMR methylation was higher in the DHA group than the control group in infants of overweight mothers (P ϭ 0.03). In addition, at H19 DMR, methylation levels were significantly lower in the DHA group than the control group in infants of normal weight mothers (P ϭ 0.01). Finally, methylation levels at IGF2/H19 imprinted regions were associated with maternal BMI. These findings suggest that epigenetic mechanisms may be modulated by DHA, with potential impacts on child growth and development. epigenetics; DHA supplementation; pregnancy; imprinted genes; maternal BMI; IGF2; H19 EPIGENETIC MODIFICATIONS ARE thought to stabilize gene expression patterns in specific cell types and to play a role in the maintenance of cell identity and differentiation fates. However, epigenetic patterns are globally reconfigured when gametes fuse to form the zygote, and gamete precursors develop and migrate in the embryo (50). Epigenetic reprogramming occurs during normal embryonic and fetal development and differentiation and might be affected by environmental exposures, resulting in long-lasting changes that could affect health and the risk of diseases in later life (2). The critical window of vulnerability to relevant environmental exposures during epigenetic reprogramming is crucial to understand the full impact of these factors on health (7). Environmental exposures that affect epigenetic reprogramming and maintenance of cell identity have been documented, including in utero exposure to dietary micronutrients (31, 43), caloric restriction (10), protein restriction (8), and cigarette smoking (30). Therefore, epigenetic regulation is regarded as a highly plausible explanation for linking dietary exposures in utero and in early life with the onset of chronic dise...

show abstract

“…In addition to being an essential amino acid, Met is also the precursor of SAM, which is required for polyamine synthesis and for various methylation processes, including DNA cytosine methylation and histone methylations. In mammals, which lack de novo folate synthesis, a Met-deficient diet causes locus-specific reduction of H3K9me2 levels (Dobosy et al, 2008), and genetic disruption of folate utilization for 5-methylTHF synthesis correlates with genomic DNA hypomethylation (Friso et al, 2002). The folate biosynthesis pathway is essentially the same in plants as in bacteria (Basset et al, 2005;Hanson and Gregory, 2011), both using dihydropterote synthase for dihydropteroic acid production.…”

Section: Discussionmentioning

confidence: 99%

Sulfamethazine Suppresses Epigenetic Silencing in Arabidopsis by Impairing Folate Synthesis

et al. 2012

View full text Add to dashboard Cite

DNA methylation is a critical, dynamically regulated epigenetic mark. Small chemicals can be valuable tools in probing cellular processes, but the set of chemicals with broad effects on epigenetic regulation is very limited. Using the Arabidopsis thaliana repressor of silencing1 mutant, in which transgenes are transcriptionally silenced, we performed chemical genetic screens and found sulfamethazine (SMZ) as a chemical suppressor of epigenetic silencing. SMZ treatment released the silencing of transgenes as well as endogenous transposons and other repetitive elements. Plants treated with SMZ exhibit substantially reduced levels of DNA methylation and histone H3 Lys-9 dimethylation, but heterochromatic siRNA levels were not affected. SMZ is a structural analog and competitive antagonist to p-aminobenzoic acid (PABA), which is a precursor of folates. SMZ decreased the plant folate pool size and caused methyl deficiency, as demonstrated by reductions in S-adenosylmethionine levels and in global DNA methylation. Exogenous application of PABA or compounds downstream in the folate biosynthesis pathway restored transcriptional silencing in SMZ-treated plants. Together, our results revealed a novel type of chemical suppressor of epigenetic silencing, which may serve as a valuable tool for studying the roles and mechanisms of epigenetic regulation and underscores an important linkage between primary metabolism and epigenetic gene regulation.

show abstract

A methyl‐deficient diet modifies histone methylation and alters Igf2 and H19 repression in the prostate

Abstract: These findings highlight the plasticity of the epigenome in an epithelial organ vulnerable to neoplastic change. They further suggest that chromatin modifications are more susceptible to methyl-deficient diets than DNA methylation at this locus.

Cited by 69 publications

References 46 publications

Aberrant epigenetic modifications in the CTCF binding domain of the IGF2/H19 gene in prostate cancer compared with benign prostate hyperplasia

Aberrant epigenetic modifications in the CTCF binding domain of the IGF2/H19 gene in prostate cancer compared with benign prostate hyperplasia

Dietary supplementation with polyunsaturated fatty acid during pregnancy modulates DNA methylation at IGF2/H19 imprinted genes and growth of infants

Sulfamethazine Suppresses Epigenetic Silencing in Arabidopsis by Impairing Folate Synthesis

Contact Info

Product

Resources

About