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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

Two CpG to TpG transitions in the first exon of DNMT3b by DNA sequencing.A. Blue arrows show the cytosines in CpG sites 1 (Chr20: 10203733) and 5 (Chr20: 10203778) of DNMT3b in the line 63, RCSs (n = 3 for each strain) and red jungle fowl (n = 1). B. Pink arrows show the two CpG to TpG transitions in the line 72. n = 3.
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pone-0002672-g004: Two CpG to TpG transitions in the first exon of DNMT3b by DNA sequencing.A. Blue arrows show the cytosines in CpG sites 1 (Chr20: 10203733) and 5 (Chr20: 10203778) of DNMT3b in the line 63, RCSs (n = 3 for each strain) and red jungle fowl (n = 1). B. Pink arrows show the two CpG to TpG transitions in the line 72. n = 3.

Mentions: The extremely low methylation levels in the CpG sites 1 and 5 of DNMT3b, compared to other 4 CpG sites, suggested that this difference could be attributed to single nucleotide polymorphisms (SNPs) between the two inbred lines. Using DNA sequencing thereafter, two CpG to TpG transitions located in the same CpG sites 1 and 5 for DNA methylation analysis, were found in line 72 (Figure 4B) but not in line 63, the RCSs, or a wild-type chicken, a red jungle fowl (Figure 4A). Taking all this into consideration, the two line-specific SNPs of DNMT3b appear to be possible genetic factors that are involved in MD tumor susceptibility in the line 72.


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)

Two CpG to TpG transitions in the first exon of DNMT3b by DNA sequencing.A. Blue arrows show the cytosines in CpG sites 1 (Chr20: 10203733) and 5 (Chr20: 10203778) of DNMT3b in the line 63, RCSs (n = 3 for each strain) and red jungle fowl (n = 1). B. Pink arrows show the two CpG to TpG transitions in the line 72. n = 3.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0002672-g004: Two CpG to TpG transitions in the first exon of DNMT3b by DNA sequencing.A. Blue arrows show the cytosines in CpG sites 1 (Chr20: 10203733) and 5 (Chr20: 10203778) of DNMT3b in the line 63, RCSs (n = 3 for each strain) and red jungle fowl (n = 1). B. Pink arrows show the two CpG to TpG transitions in the line 72. n = 3.
Mentions: The extremely low methylation levels in the CpG sites 1 and 5 of DNMT3b, compared to other 4 CpG sites, suggested that this difference could be attributed to single nucleotide polymorphisms (SNPs) between the two inbred lines. Using DNA sequencing thereafter, two CpG to TpG transitions located in the same CpG sites 1 and 5 for DNA methylation analysis, were found in line 72 (Figure 4B) but not in line 63, the RCSs, or a wild-type chicken, a red jungle fowl (Figure 4A). Taking all this into consideration, the two line-specific SNPs of DNMT3b appear to be possible genetic factors that are involved in MD tumor susceptibility in the line 72.

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