Limits...
Inactive X chromosome-specific reduction in placental DNA methylation.

Cotton AM, Avila L, Penaherrera MS, Affleck JG, Robinson WP, Brown CJ - Hum. Mol. Genet. (2009)

Bottom Line: Genome-wide levels of DNA methylation vary between tissues, and compared with other tissues, the placenta has been reported to demonstrate a global decrease in methylation as well as decreased methylation of X-linked promoters.Thus placental hypomethylation relative to blood is observed globally at repetitive elements as well as across the X.The decrease in X-linked placental methylation is consistently greater in females than males and implicates an inactive X specific loss of methylation in the placenta.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.

ABSTRACT
Genome-wide levels of DNA methylation vary between tissues, and compared with other tissues, the placenta has been reported to demonstrate a global decrease in methylation as well as decreased methylation of X-linked promoters. Methylation is one of many features that differentiate the active and inactive X, and it is well established that CpG island promoters on the inactive X are hypermethylated. We now report a detailed analysis of methylation at different regions across the X in male and female placenta and blood. A significant (P < 0.001) placental hypomethylation of LINE1 elements was observed in both males and females. Relative to blood placental promoter hypomethylation was only observed for X-linked, not autosomal promoters, and was significant for females (P < 0.0001) not males (P = 0.9266). In blood, X-linked CpG island promoters were shown to have moderate female methylation (66% across 70 assays) and low (23%) methylation in males. A similar methylation pattern in blood was observed for approximately 20% of non-island promoters as well as 50% of the intergenic or intragenic CpG islands, the latter is likely due to the presence of unannotated promoters. Both intragenic and intergenic regions showed similarly high methylation levels in male and female blood (68 and 66%) while placental methylation of these regions was lower, particularly in females. Thus placental hypomethylation relative to blood is observed globally at repetitive elements as well as across the X. The decrease in X-linked placental methylation is consistently greater in females than males and implicates an inactive X specific loss of methylation in the placenta.

Show MeSH
Summary of methylation analyses showing placental reduction in methylation predominately on the Xi. Data from both Illumina and pyrosequencing are combined and shown separately for CpG island (HC & IC) assays and non-island (LC) assays in promoter regions, intragenic regions (includes both introns and exons) and intergenic regions. In order to combine Illumina GoldenGate data (which is only for promoter regions), we converted beta-values to percent methylation. These values were consistent with pyrosequencing data at the low range, but generally higher than pyrosequencing in the midrange, accounting for the Xi value over 1 for promoters. Percent methylation is the average of all CpGs in the indicated region. Percent methylation is divided into Xa and Xi with grey bars representing methylation in blood and black bars for placenta with the average percent methylation value written in each bar. The summary of the methylation trends for the different regions is described below each bar graph. Significance calculated using Mann–Whitney test with significance shown as P = 0.01 to 0.05 (*), P = 0.01 to 0.001 (**) and P < 0.001 (***).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2742397&req=5

DDP299F4: Summary of methylation analyses showing placental reduction in methylation predominately on the Xi. Data from both Illumina and pyrosequencing are combined and shown separately for CpG island (HC & IC) assays and non-island (LC) assays in promoter regions, intragenic regions (includes both introns and exons) and intergenic regions. In order to combine Illumina GoldenGate data (which is only for promoter regions), we converted beta-values to percent methylation. These values were consistent with pyrosequencing data at the low range, but generally higher than pyrosequencing in the midrange, accounting for the Xi value over 1 for promoters. Percent methylation is the average of all CpGs in the indicated region. Percent methylation is divided into Xa and Xi with grey bars representing methylation in blood and black bars for placenta with the average percent methylation value written in each bar. The summary of the methylation trends for the different regions is described below each bar graph. Significance calculated using Mann–Whitney test with significance shown as P = 0.01 to 0.05 (*), P = 0.01 to 0.001 (**) and P < 0.001 (***).

Mentions: Figure 4 summarizes the changes in placental X-linked methylation and illustrates that not only is placenta less methylated than blood but the majority of this difference is due to the Xi. The Xi appeared to show the greatest decrease in methylation at promoters, however, the limited number of assays and the combination of two methylation detection techniques precludes a definitive conclusion as to the degree of Xi placental hypomethylation between regions. MeXiP is the clear pattern for X-linked CpG island promoters, as well as a subset of non-island promoters. This trend is maintained for the intragenic and intergenic regions for CpG islands, likely due to the presence of unannotated gene promoters. The exclusion of possible unannotated promoters (regions demonstrating MeXiP) resulted in higher intragenic and intergenic methylation on the Xa than the Xi for both blood and placenta regardless of CpG density.


Inactive X chromosome-specific reduction in placental DNA methylation.

Cotton AM, Avila L, Penaherrera MS, Affleck JG, Robinson WP, Brown CJ - Hum. Mol. Genet. (2009)

Summary of methylation analyses showing placental reduction in methylation predominately on the Xi. Data from both Illumina and pyrosequencing are combined and shown separately for CpG island (HC & IC) assays and non-island (LC) assays in promoter regions, intragenic regions (includes both introns and exons) and intergenic regions. In order to combine Illumina GoldenGate data (which is only for promoter regions), we converted beta-values to percent methylation. These values were consistent with pyrosequencing data at the low range, but generally higher than pyrosequencing in the midrange, accounting for the Xi value over 1 for promoters. Percent methylation is the average of all CpGs in the indicated region. Percent methylation is divided into Xa and Xi with grey bars representing methylation in blood and black bars for placenta with the average percent methylation value written in each bar. The summary of the methylation trends for the different regions is described below each bar graph. Significance calculated using Mann–Whitney test with significance shown as P = 0.01 to 0.05 (*), P = 0.01 to 0.001 (**) and P < 0.001 (***).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2742397&req=5

DDP299F4: Summary of methylation analyses showing placental reduction in methylation predominately on the Xi. Data from both Illumina and pyrosequencing are combined and shown separately for CpG island (HC & IC) assays and non-island (LC) assays in promoter regions, intragenic regions (includes both introns and exons) and intergenic regions. In order to combine Illumina GoldenGate data (which is only for promoter regions), we converted beta-values to percent methylation. These values were consistent with pyrosequencing data at the low range, but generally higher than pyrosequencing in the midrange, accounting for the Xi value over 1 for promoters. Percent methylation is the average of all CpGs in the indicated region. Percent methylation is divided into Xa and Xi with grey bars representing methylation in blood and black bars for placenta with the average percent methylation value written in each bar. The summary of the methylation trends for the different regions is described below each bar graph. Significance calculated using Mann–Whitney test with significance shown as P = 0.01 to 0.05 (*), P = 0.01 to 0.001 (**) and P < 0.001 (***).
Mentions: Figure 4 summarizes the changes in placental X-linked methylation and illustrates that not only is placenta less methylated than blood but the majority of this difference is due to the Xi. The Xi appeared to show the greatest decrease in methylation at promoters, however, the limited number of assays and the combination of two methylation detection techniques precludes a definitive conclusion as to the degree of Xi placental hypomethylation between regions. MeXiP is the clear pattern for X-linked CpG island promoters, as well as a subset of non-island promoters. This trend is maintained for the intragenic and intergenic regions for CpG islands, likely due to the presence of unannotated gene promoters. The exclusion of possible unannotated promoters (regions demonstrating MeXiP) resulted in higher intragenic and intergenic methylation on the Xa than the Xi for both blood and placenta regardless of CpG density.

Bottom Line: Genome-wide levels of DNA methylation vary between tissues, and compared with other tissues, the placenta has been reported to demonstrate a global decrease in methylation as well as decreased methylation of X-linked promoters.Thus placental hypomethylation relative to blood is observed globally at repetitive elements as well as across the X.The decrease in X-linked placental methylation is consistently greater in females than males and implicates an inactive X specific loss of methylation in the placenta.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.

ABSTRACT
Genome-wide levels of DNA methylation vary between tissues, and compared with other tissues, the placenta has been reported to demonstrate a global decrease in methylation as well as decreased methylation of X-linked promoters. Methylation is one of many features that differentiate the active and inactive X, and it is well established that CpG island promoters on the inactive X are hypermethylated. We now report a detailed analysis of methylation at different regions across the X in male and female placenta and blood. A significant (P < 0.001) placental hypomethylation of LINE1 elements was observed in both males and females. Relative to blood placental promoter hypomethylation was only observed for X-linked, not autosomal promoters, and was significant for females (P < 0.0001) not males (P = 0.9266). In blood, X-linked CpG island promoters were shown to have moderate female methylation (66% across 70 assays) and low (23%) methylation in males. A similar methylation pattern in blood was observed for approximately 20% of non-island promoters as well as 50% of the intergenic or intragenic CpG islands, the latter is likely due to the presence of unannotated promoters. Both intragenic and intergenic regions showed similarly high methylation levels in male and female blood (68 and 66%) while placental methylation of these regions was lower, particularly in females. Thus placental hypomethylation relative to blood is observed globally at repetitive elements as well as across the X. The decrease in X-linked placental methylation is consistently greater in females than males and implicates an inactive X specific loss of methylation in the placenta.

Show MeSH