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An integrated epigenetic and genetic analysis of DNA methyltransferase genes (DNMTs) in tumor resistant and susceptible chicken lines.

Yu Y, Zhang H, Tian F, Zhang W, Fang H, Song J - PLoS ONE (2008)

Bottom Line: However, two line-specific DNA transition mutations, CpG-->TpG (Chr20:10203733 and 10203778), were discovered in line 7(2) compared to the line 6(3) and RCSs.Moreover, we developed a novel method that can effectively test the significance of DNA methylation patterns consisting of continuous CpG sites.Taken together, these results highlight the potential of epigenetic alterations in DNMT1 and DNMT3a, as well as the DNA mutations in DNMT3b, as epigenetic and genetic factors to neoplastic diseases of chickens.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland, United State of America.

ABSTRACT
Both epigenetic alterations and genetic variations play essential roles in tumorigenesis. The epigenetic modification of DNA methylation is catalyzed and maintained by the DNA methyltransferases (DNMT3a, DNMT3b and DNMT1). DNA mutations and DNA methylation profiles of DNMTs themselves and their relationships with chicken neoplastic disease resistance and susceptibility are not yet defined. In the present study, we analyzed the complexity of the DNA methylation variations and DNA mutations in the first exon of three DNMTs genes over generations, tissues, and ages among chickens of two highly inbred White Leghorn lines, Marek's disease-resistant line 6(3) and -susceptible line 7(2), and six recombinant congenic strains (RCSs). Among them, tissue-specific methylation patterns of DNMT3a were disclosed in spleen, liver, and hypothalamus in lines 6(3) and 7(2). The methylation level of DNMT3b on four CpG sites was not significantly different among four tissues of the two lines. However, two line-specific DNA transition mutations, CpG-->TpG (Chr20:10203733 and 10203778), were discovered in line 7(2) compared to the line 6(3) and RCSs. The methylation contents of DNMT1 in blood cell showed significant epimutations in the first CpG site among the two inbred lines and the six RCSs (P<0.05). Age-specific methylation of DNMT1 was detected in comparisons between 15 month-old and 2 month-old chickens in both lines except in spleen samples from line 7(2). No DNA mutations were discovered on the studied regions of DNMT1 and DNMT3a among the two lines and the six RCSs. Moreover, we developed a novel method that can effectively test the significance of DNA methylation patterns consisting of continuous CpG sites. Taken together, these results highlight the potential of epigenetic alterations in DNMT1 and DNMT3a, as well as the DNA mutations in DNMT3b, as epigenetic and genetic factors to neoplastic diseases of chickens.

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Related in: MedlinePlus

DNA methylation variations of DNMT1 in spleen (A, B) and liver (C, D) at 15 months and 8 weeks old in line 63 and line 72. * P<0.05. n = 5 for each line.
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pone-0002672-g009: DNA methylation variations of DNMT1 in spleen (A, B) and liver (C, D) at 15 months and 8 weeks old in line 63 and line 72. * P<0.05. n = 5 for each line.

Mentions: To maintain methylation patterns in daughter cells during DNA replication, the unmethylated daughter CpG site opposite to a methylated parental CpG site must be methylated by the maintenance methyltransferase, DNMT1. It is important, therefore, to investigate the methylation status of DNMT1 and compare it with the de novo methyltransferases in the unique chicken population. We quantitatively measured DNA methylation levels of four CpG sites in the exon1 region of DNMT1 in four tissues at three age stages. Our results indicated that DNMT1 had a similar methylation pattern in the spleen, liver, and hypothalamus (Figure 8A, 8B and 8C) between the two inbred lines at 15 months of age, whereas the CpG site 1 in blood cell showed a significant epimutation among the two parental lines and the six RCSs (P<0.05) (Figure 8D) at 12 months of age. Interestingly, comparing the methylation levels of DNMT1 between the two ages, we found that the methylation level of the CpG site 1 at two months of age was lower than that at 15 months of age in spleen (P<0.05) (Figure 9A) and liver (Figure 9C and 9D) for both the parental lines except in spleen of the line 72 (Figure 9B). The results indicated that DNMT1 is an epimutation gene with age-specific methylation patterns in the chickens.


An integrated epigenetic and genetic analysis of DNA methyltransferase genes (DNMTs) in tumor resistant and susceptible chicken lines.

Yu Y, Zhang H, Tian F, Zhang W, Fang H, Song J - PLoS ONE (2008)

DNA methylation variations of DNMT1 in spleen (A, B) and liver (C, D) at 15 months and 8 weeks old in line 63 and line 72. * P<0.05. n = 5 for each line.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2481300&req=5

pone-0002672-g009: DNA methylation variations of DNMT1 in spleen (A, B) and liver (C, D) at 15 months and 8 weeks old in line 63 and line 72. * P<0.05. n = 5 for each line.
Mentions: To maintain methylation patterns in daughter cells during DNA replication, the unmethylated daughter CpG site opposite to a methylated parental CpG site must be methylated by the maintenance methyltransferase, DNMT1. It is important, therefore, to investigate the methylation status of DNMT1 and compare it with the de novo methyltransferases in the unique chicken population. We quantitatively measured DNA methylation levels of four CpG sites in the exon1 region of DNMT1 in four tissues at three age stages. Our results indicated that DNMT1 had a similar methylation pattern in the spleen, liver, and hypothalamus (Figure 8A, 8B and 8C) between the two inbred lines at 15 months of age, whereas the CpG site 1 in blood cell showed a significant epimutation among the two parental lines and the six RCSs (P<0.05) (Figure 8D) at 12 months of age. Interestingly, comparing the methylation levels of DNMT1 between the two ages, we found that the methylation level of the CpG site 1 at two months of age was lower than that at 15 months of age in spleen (P<0.05) (Figure 9A) and liver (Figure 9C and 9D) for both the parental lines except in spleen of the line 72 (Figure 9B). The results indicated that DNMT1 is an epimutation gene with age-specific methylation patterns in the chickens.

Bottom Line: However, two line-specific DNA transition mutations, CpG-->TpG (Chr20:10203733 and 10203778), were discovered in line 7(2) compared to the line 6(3) and RCSs.Moreover, we developed a novel method that can effectively test the significance of DNA methylation patterns consisting of continuous CpG sites.Taken together, these results highlight the potential of epigenetic alterations in DNMT1 and DNMT3a, as well as the DNA mutations in DNMT3b, as epigenetic and genetic factors to neoplastic diseases of chickens.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland, United State of America.

ABSTRACT
Both epigenetic alterations and genetic variations play essential roles in tumorigenesis. The epigenetic modification of DNA methylation is catalyzed and maintained by the DNA methyltransferases (DNMT3a, DNMT3b and DNMT1). DNA mutations and DNA methylation profiles of DNMTs themselves and their relationships with chicken neoplastic disease resistance and susceptibility are not yet defined. In the present study, we analyzed the complexity of the DNA methylation variations and DNA mutations in the first exon of three DNMTs genes over generations, tissues, and ages among chickens of two highly inbred White Leghorn lines, Marek's disease-resistant line 6(3) and -susceptible line 7(2), and six recombinant congenic strains (RCSs). Among them, tissue-specific methylation patterns of DNMT3a were disclosed in spleen, liver, and hypothalamus in lines 6(3) and 7(2). The methylation level of DNMT3b on four CpG sites was not significantly different among four tissues of the two lines. However, two line-specific DNA transition mutations, CpG-->TpG (Chr20:10203733 and 10203778), were discovered in line 7(2) compared to the line 6(3) and RCSs. The methylation contents of DNMT1 in blood cell showed significant epimutations in the first CpG site among the two inbred lines and the six RCSs (P<0.05). Age-specific methylation of DNMT1 was detected in comparisons between 15 month-old and 2 month-old chickens in both lines except in spleen samples from line 7(2). No DNA mutations were discovered on the studied regions of DNMT1 and DNMT3a among the two lines and the six RCSs. Moreover, we developed a novel method that can effectively test the significance of DNA methylation patterns consisting of continuous CpG sites. Taken together, these results highlight the potential of epigenetic alterations in DNMT1 and DNMT3a, as well as the DNA mutations in DNMT3b, as epigenetic and genetic factors to neoplastic diseases of chickens.

Show MeSH
Related in: MedlinePlus