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Quantitative evaluation of DNA methylation patterns for ALVE and TVB genes in a neoplastic disease susceptible and resistant chicken model.

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

Bottom Line: CpG methylation contents of the ALVE regions were significantly lower in line 6(3) than in line 7(2) in all tissues (P < 0.01) except the ALVE region 3/4 in liver.RNA expressions of ALVE regions 2 and 3 (PPT-U3) were significantly higher in line 6(3) than in line 7(2) (P < 0.01).The methylation level of the promoter region in the TVB was significantly different in blood (P < 0.05) and hypothalamus (P < 0.0001), respectively.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal & Avian Sciences, University of Maryland, College Park, Maryland, USA.

ABSTRACT
Chicken endogenous viruses, ALVE (Avian Leukosis Virus subgroup E), are inherited as LTR (long terminal repeat) retrotransposons, which are negatively correlated with disease resistance, and any changes in DNA methylation may contribute to the susceptibility to neoplastic disease. The relationship between ALVE methylation status and neoplastic disease in the chicken is undefined. White Leghorn inbred lines 7(2) and 6(3) at the ADOL have been respectively selected for resistance and susceptibility to tumors that are induced by avian viruses. In this study, the DNA methylation patterns of 3 approximately 6 CpG sites of four conserved regions in ALVE, including one unique region in ALVE1, the promoter region in the TVB (tumor virus receptor of ALV subgroup B, D and E) locus, were analyzed in the two lines using pyrosequencing methods in four tissues, i.e., liver, spleen, blood and hypothalamus. A significant CpG hypermethylation level was seen in line 7(2) in all four tissues, e.g., 91.86 +/- 1.63% for ALVE region2 in blood, whereas the same region was hemimethylated (46.16 +/- 2.56%) in line 6(3). CpG methylation contents of the ALVE regions were significantly lower in line 6(3) than in line 7(2) in all tissues (P < 0.01) except the ALVE region 3/4 in liver. RNA expressions of ALVE regions 2 and 3 (PPT-U3) were significantly higher in line 6(3) than in line 7(2) (P < 0.01). The methylation levels of six recombinant congenic strains (RCSs) closely resembled to the background line 6(3) in ALVE-region 2, which imply the methylation pattern of ALVE-region 2 may be a biomarker in resistant disease breeding. The methylation level of the promoter region in the TVB was significantly different in blood (P < 0.05) and hypothalamus (P < 0.0001), respectively. Our data disclosed a hypermethylation pattern of ALVE that may be relevant for resistance against ALV induced tumors in chickens.

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Results of quantitative DNA methylation analysis of inbred lines 63 and 72 in promoter region of TVB in spleen, liver, hypothalamus and blood.n = 5 for each line. **P<0.0001, * P<0.05.
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pone-0001731-g007: Results of quantitative DNA methylation analysis of inbred lines 63 and 72 in promoter region of TVB in spleen, liver, hypothalamus and blood.n = 5 for each line. **P<0.0001, * P<0.05.

Mentions: The tumor virus B (TVB) locus is an important gene encoding the cellular receptor of avian leukosis virus, different TVB alleles can encode different receptors permitting infection by exogenous ALVB, or ALVD and endogenous ALVE. To uncover epigenetics factors contributing to susceptibility or resistance of neoplastic disease in chickens, we examined the DNA methylation status of the TVB gene. Figure 2D shows the presentative pyrograms for three CpG sites in the promoter region of the TVB gene in the hypothalamus tissue of both lines. The results show that the methylation level of TVB promoter was significantly higher in line 72 than that in line 63 (P<0.0001, Figure 7). Unlike the consensus methylation trends of the ALVEs regions 1 and 2 (Figure 3A and 3B), the promoter region of TVB shows tissue-specific methylation patterns (Figure 7) similar to the promoter region 3/4 in ALVEs (Figure 3C). As shown in Figure 7, CpG site 3 in the promoter region of TVB showed a hemimethylated pattern in the spleen, liver and hypothalamus in both lines, whereas a hypomethylated pattern was disclosed in the blood. In addition, CpG site 3 of TVB in blood was significantly higher in line 72 than in line 63 (P<0.05). We found some variations regarding methylation contents among the 6 RCSs, especially for CpG sites 2 and 3, although the methylation patterns of RCSs were similar to background line 63 (Figure 8).


Quantitative evaluation of DNA methylation patterns for ALVE and TVB genes in a neoplastic disease susceptible and resistant chicken model.

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

Results of quantitative DNA methylation analysis of inbred lines 63 and 72 in promoter region of TVB in spleen, liver, hypothalamus and blood.n = 5 for each line. **P<0.0001, * P<0.05.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2254315&req=5

pone-0001731-g007: Results of quantitative DNA methylation analysis of inbred lines 63 and 72 in promoter region of TVB in spleen, liver, hypothalamus and blood.n = 5 for each line. **P<0.0001, * P<0.05.
Mentions: The tumor virus B (TVB) locus is an important gene encoding the cellular receptor of avian leukosis virus, different TVB alleles can encode different receptors permitting infection by exogenous ALVB, or ALVD and endogenous ALVE. To uncover epigenetics factors contributing to susceptibility or resistance of neoplastic disease in chickens, we examined the DNA methylation status of the TVB gene. Figure 2D shows the presentative pyrograms for three CpG sites in the promoter region of the TVB gene in the hypothalamus tissue of both lines. The results show that the methylation level of TVB promoter was significantly higher in line 72 than that in line 63 (P<0.0001, Figure 7). Unlike the consensus methylation trends of the ALVEs regions 1 and 2 (Figure 3A and 3B), the promoter region of TVB shows tissue-specific methylation patterns (Figure 7) similar to the promoter region 3/4 in ALVEs (Figure 3C). As shown in Figure 7, CpG site 3 in the promoter region of TVB showed a hemimethylated pattern in the spleen, liver and hypothalamus in both lines, whereas a hypomethylated pattern was disclosed in the blood. In addition, CpG site 3 of TVB in blood was significantly higher in line 72 than in line 63 (P<0.05). We found some variations regarding methylation contents among the 6 RCSs, especially for CpG sites 2 and 3, although the methylation patterns of RCSs were similar to background line 63 (Figure 8).

Bottom Line: CpG methylation contents of the ALVE regions were significantly lower in line 6(3) than in line 7(2) in all tissues (P < 0.01) except the ALVE region 3/4 in liver.RNA expressions of ALVE regions 2 and 3 (PPT-U3) were significantly higher in line 6(3) than in line 7(2) (P < 0.01).The methylation level of the promoter region in the TVB was significantly different in blood (P < 0.05) and hypothalamus (P < 0.0001), respectively.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal & Avian Sciences, University of Maryland, College Park, Maryland, USA.

ABSTRACT
Chicken endogenous viruses, ALVE (Avian Leukosis Virus subgroup E), are inherited as LTR (long terminal repeat) retrotransposons, which are negatively correlated with disease resistance, and any changes in DNA methylation may contribute to the susceptibility to neoplastic disease. The relationship between ALVE methylation status and neoplastic disease in the chicken is undefined. White Leghorn inbred lines 7(2) and 6(3) at the ADOL have been respectively selected for resistance and susceptibility to tumors that are induced by avian viruses. In this study, the DNA methylation patterns of 3 approximately 6 CpG sites of four conserved regions in ALVE, including one unique region in ALVE1, the promoter region in the TVB (tumor virus receptor of ALV subgroup B, D and E) locus, were analyzed in the two lines using pyrosequencing methods in four tissues, i.e., liver, spleen, blood and hypothalamus. A significant CpG hypermethylation level was seen in line 7(2) in all four tissues, e.g., 91.86 +/- 1.63% for ALVE region2 in blood, whereas the same region was hemimethylated (46.16 +/- 2.56%) in line 6(3). CpG methylation contents of the ALVE regions were significantly lower in line 6(3) than in line 7(2) in all tissues (P < 0.01) except the ALVE region 3/4 in liver. RNA expressions of ALVE regions 2 and 3 (PPT-U3) were significantly higher in line 6(3) than in line 7(2) (P < 0.01). The methylation levels of six recombinant congenic strains (RCSs) closely resembled to the background line 6(3) in ALVE-region 2, which imply the methylation pattern of ALVE-region 2 may be a biomarker in resistant disease breeding. The methylation level of the promoter region in the TVB was significantly different in blood (P < 0.05) and hypothalamus (P < 0.0001), respectively. Our data disclosed a hypermethylation pattern of ALVE that may be relevant for resistance against ALV induced tumors in chickens.

Show MeSH
Related in: MedlinePlus