Limits...
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.

Show MeSH

Related in: MedlinePlus

DNA methylation profiles of DNMT3b in spleen (A) and liver (B) at 15 months and 8 weeks old in the line 63. n = 5 for each line.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2481300&req=5

pone-0002672-g003: DNA methylation profiles of DNMT3b in spleen (A) and liver (B) at 15 months and 8 weeks old in the line 63. n = 5 for each line.

Mentions: To further check the variations of DNA methylation patterns of the three chicken DNMTs, we examined DNA methylation levels of DNMT3b in four tissues at two ages of the two lines. Figure 2A, 2B, and 2C exhibited the methylation profiles of the DNMT3b in the spleen, liver and hypothalamus between lines 63 and 72 at 15 months of age. We found that the methylation levels of DNMT3b at CpG sites 1 and 5 were significantly higher in line 63 than in line 72 (P<0.01). We thereafter examined the methylation status of DNMT3b in spleen and liver in line 63 chickens of 2 months of age. As shown in Figure 3A and 3B, the methylation level of DNMT3b gene in spleen and liver shows a similar pattern in line 63 chickens of 2 and 15 months of ages (P>0.05). The results implied that the DNA methylation of DNMT3b does not have age specificity in line 63.


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 profiles of DNMT3b in spleen (A) and liver (B) at 15 months and 8 weeks old in the line 63. n = 5 for each line.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0002672-g003: DNA methylation profiles of DNMT3b in spleen (A) and liver (B) at 15 months and 8 weeks old in the line 63. n = 5 for each line.
Mentions: To further check the variations of DNA methylation patterns of the three chicken DNMTs, we examined DNA methylation levels of DNMT3b in four tissues at two ages of the two lines. Figure 2A, 2B, and 2C exhibited the methylation profiles of the DNMT3b in the spleen, liver and hypothalamus between lines 63 and 72 at 15 months of age. We found that the methylation levels of DNMT3b at CpG sites 1 and 5 were significantly higher in line 63 than in line 72 (P<0.01). We thereafter examined the methylation status of DNMT3b in spleen and liver in line 63 chickens of 2 months of age. As shown in Figure 3A and 3B, the methylation level of DNMT3b gene in spleen and liver shows a similar pattern in line 63 chickens of 2 and 15 months of ages (P>0.05). The results implied that the DNA methylation of DNMT3b does not have age specificity in line 63.

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