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Features of methylation and gene expression in the promoter-associated CpG islands using human methylome data.

Du X, Han L, Guo AY, Zhao Z - Comp. Funct. Genomics (2012)

Bottom Line: In this study, we compared the features of CpG islands identified by several major algorithms by setting the parameter cutoff values in order to obtain a similar number of CpG islands in a genome.In addition, we used the genome-wide base-resolution methylation profile in two cell lines to show that genes with a lower methylation level at the promoter-associated CpG islands tend to express in more tissues and have stronger expression.Our results validated that the DNA methylation of promoter-associated CpG islands suppresses gene expression at the genome level.

View Article: PubMed Central - PubMed

Affiliation: College of Life Sciences, Central China Normal University, Wuhan 430079, China.

ABSTRACT
CpG islands are typically located in the 5' end of genes and considered as gene markers because they play important roles in gene regulation via epigenetic change. In this study, we compared the features of CpG islands identified by several major algorithms by setting the parameter cutoff values in order to obtain a similar number of CpG islands in a genome. This approach allows us to systematically compare the methylation and gene expression patterns in the identified CpG islands. We found that Takai and Jones' algorithm tends to identify longer CpG islands but with weaker CpG island features (e.g., lower GC content and lower ratio of the observed over expected CpGs) and higher methylation level. Conversely, the CpG clusters identified by Hackenberg et al.'s algorithm using stringent criteria are shorter and have stronger features and lower methylation level. In addition, we used the genome-wide base-resolution methylation profile in two cell lines to show that genes with a lower methylation level at the promoter-associated CpG islands tend to express in more tissues and have stronger expression. Our results validated that the DNA methylation of promoter-associated CpG islands suppresses gene expression at the genome level.

No MeSH data available.


Correlation between the number of expressed tissues and expression strength.
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Related In: Results  -  Collection


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fig5: Correlation between the number of expressed tissues and expression strength.

Mentions: To further study the correlation between the methylation of promoter-associated CpG islands and gene expression strength, we used the average expression level across the 79 human tissues in the second version of the Gene Atlas dataset to represent the expression strength of a gene. In the human H1 cell line, the methylation level of the promoter-associated CpG islands in the genes with a strong expression strength (log2 expression value > 9) was much lower than those with a weak expression strength (log2 expression value < 6) (Figure 4(a)). One should note that the methylation level of promoter-associated CpG islands in genes whose expression strength values are in the range of 9–12 is similar to that of genes whose expression strength values are greater than 12. Again, a similar trend was observed when we used the methylation data from the IMR90 cell line (Figure 4(b)). Furthermore, we found a significant positive correlation between broadness of expression and expression strength (Pearson correlation r = 0.859, P < .2 × 10−16, Figure 5). This finding explained the consistency between broadness of expression and strength of expression.


Features of methylation and gene expression in the promoter-associated CpG islands using human methylome data.

Du X, Han L, Guo AY, Zhao Z - Comp. Funct. Genomics (2012)

Correlation between the number of expressed tissues and expression strength.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3303704&req=5

fig5: Correlation between the number of expressed tissues and expression strength.
Mentions: To further study the correlation between the methylation of promoter-associated CpG islands and gene expression strength, we used the average expression level across the 79 human tissues in the second version of the Gene Atlas dataset to represent the expression strength of a gene. In the human H1 cell line, the methylation level of the promoter-associated CpG islands in the genes with a strong expression strength (log2 expression value > 9) was much lower than those with a weak expression strength (log2 expression value < 6) (Figure 4(a)). One should note that the methylation level of promoter-associated CpG islands in genes whose expression strength values are in the range of 9–12 is similar to that of genes whose expression strength values are greater than 12. Again, a similar trend was observed when we used the methylation data from the IMR90 cell line (Figure 4(b)). Furthermore, we found a significant positive correlation between broadness of expression and expression strength (Pearson correlation r = 0.859, P < .2 × 10−16, Figure 5). This finding explained the consistency between broadness of expression and strength of expression.

Bottom Line: In this study, we compared the features of CpG islands identified by several major algorithms by setting the parameter cutoff values in order to obtain a similar number of CpG islands in a genome.In addition, we used the genome-wide base-resolution methylation profile in two cell lines to show that genes with a lower methylation level at the promoter-associated CpG islands tend to express in more tissues and have stronger expression.Our results validated that the DNA methylation of promoter-associated CpG islands suppresses gene expression at the genome level.

View Article: PubMed Central - PubMed

Affiliation: College of Life Sciences, Central China Normal University, Wuhan 430079, China.

ABSTRACT
CpG islands are typically located in the 5' end of genes and considered as gene markers because they play important roles in gene regulation via epigenetic change. In this study, we compared the features of CpG islands identified by several major algorithms by setting the parameter cutoff values in order to obtain a similar number of CpG islands in a genome. This approach allows us to systematically compare the methylation and gene expression patterns in the identified CpG islands. We found that Takai and Jones' algorithm tends to identify longer CpG islands but with weaker CpG island features (e.g., lower GC content and lower ratio of the observed over expected CpGs) and higher methylation level. Conversely, the CpG clusters identified by Hackenberg et al.'s algorithm using stringent criteria are shorter and have stronger features and lower methylation level. In addition, we used the genome-wide base-resolution methylation profile in two cell lines to show that genes with a lower methylation level at the promoter-associated CpG islands tend to express in more tissues and have stronger expression. Our results validated that the DNA methylation of promoter-associated CpG islands suppresses gene expression at the genome level.

No MeSH data available.