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Common altered epigenomic domains in cancer cells: characterization and subtle variations.

Tsai YC, Chiao CH, Chang IY, Chen DT, Liu TT, Hua K, Chang CH, Hsu MT - Cancers (Basel) (2011)

Bottom Line: Furthermore, they are inversely correlated with the H3K9Ac landscape and gene expression as measured in MCF-7 cells.Treatment with drugs resulted in en-bloc changes to the methylation domains.Taken together these results suggest that the human genome is organized in epigenomic domains that contain various different types of genes and imply that there are cis- and trans-regulators that control these domain-wide epigenetic changes and hence gene expression in the human genome.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Biology and Biochemistry, National Yang Ming University, No.155, Sec.2, Linong Street, Taipei, 112 Taiwan. mth@ym.edu.tw.

ABSTRACT
We have previously identified large megabase-sized hypomethylated zones in the genome of the breast cancer cell line MCF-7 using the TspRI-ExoIII technique. In this report, we used a more convenient high throughput method for mapping the hypomethylated zones in a number of human tumor genomes simultaneously. The method was validated by the bisulfite sequencing of 39 randomly chosen sites in a demethylated domain and by bisulfite genome-wide sequencing of the MCF-7 genome. This showed that the genomes of the various tumor cell lines, as well as some primary tumors, exhibit common hypomethylated domains. Interestingly, these hypomethylated domains are correlated with low CpG density distribution genome-wide, together with the histone H3K27Me3 landscape. Furthermore, they are inversely correlated with the H3K9Ac landscape and gene expression as measured in MCF-7 cells. Treatment with drugs resulted in en-bloc changes to the methylation domains. A close examination of the methylation domains found differences between non-invasive and invasive tumors with respect to tumorigenesis related genes. Taken together these results suggest that the human genome is organized in epigenomic domains that contain various different types of genes and imply that there are cis- and trans-regulators that control these domain-wide epigenetic changes and hence gene expression in the human genome. The hypomethylated domains are located in gene deserts that contain mainly tissue-specific genes and therefore we hypothesize that tumor cells keep these regions demethylated and silenced in order to save energy and resources and allow higher levels of cell proliferation and better survival (a thrifty tumor genome hypothesis).

No MeSH data available.


Related in: MedlinePlus

Degree of hypomethylation across the various chromosomes of the MCF-7 genome. The relative number of probes in the array that are hypermethylated (blue) and hypomethylated (red) are plotted for each chromosome (Upper graph). The ratio of the hypomethylated probes to the hypermethylated probes are shown in the lower graph. The X chromosome and chromosome 4 are the most hypomethylated chromosomes, whereas chromosomes 7 and 22 are the most hypermethylated chromosomes.
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f3-cancers-03-01996: Degree of hypomethylation across the various chromosomes of the MCF-7 genome. The relative number of probes in the array that are hypermethylated (blue) and hypomethylated (red) are plotted for each chromosome (Upper graph). The ratio of the hypomethylated probes to the hypermethylated probes are shown in the lower graph. The X chromosome and chromosome 4 are the most hypomethylated chromosomes, whereas chromosomes 7 and 22 are the most hypermethylated chromosomes.

Mentions: Using the new McrBC method we determined the methylome profiles of 13 human tumor genomes; these included breast, liver, brain and lung tumor cell lines as well as various primary tumor tissues. As shown in Figure 2 and in the supplementary data, all the tumor genomes, including the primary tumors, contained similar hypomethylated domains. As shown in Figure 3, chromosome 22 is the most hypermethylated of all the human chromosomes, whereas the X chromosome and chromosome 4 are the most hypomethylated. It is interesting to note that the common tumor methylome pattern across the various genomes has an interesting one-to-one correspondence with the CpG dinucleotide distribution density in the genome and with gene density (Figure 4).


Common altered epigenomic domains in cancer cells: characterization and subtle variations.

Tsai YC, Chiao CH, Chang IY, Chen DT, Liu TT, Hua K, Chang CH, Hsu MT - Cancers (Basel) (2011)

Degree of hypomethylation across the various chromosomes of the MCF-7 genome. The relative number of probes in the array that are hypermethylated (blue) and hypomethylated (red) are plotted for each chromosome (Upper graph). The ratio of the hypomethylated probes to the hypermethylated probes are shown in the lower graph. The X chromosome and chromosome 4 are the most hypomethylated chromosomes, whereas chromosomes 7 and 22 are the most hypermethylated chromosomes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3757401&req=5

f3-cancers-03-01996: Degree of hypomethylation across the various chromosomes of the MCF-7 genome. The relative number of probes in the array that are hypermethylated (blue) and hypomethylated (red) are plotted for each chromosome (Upper graph). The ratio of the hypomethylated probes to the hypermethylated probes are shown in the lower graph. The X chromosome and chromosome 4 are the most hypomethylated chromosomes, whereas chromosomes 7 and 22 are the most hypermethylated chromosomes.
Mentions: Using the new McrBC method we determined the methylome profiles of 13 human tumor genomes; these included breast, liver, brain and lung tumor cell lines as well as various primary tumor tissues. As shown in Figure 2 and in the supplementary data, all the tumor genomes, including the primary tumors, contained similar hypomethylated domains. As shown in Figure 3, chromosome 22 is the most hypermethylated of all the human chromosomes, whereas the X chromosome and chromosome 4 are the most hypomethylated. It is interesting to note that the common tumor methylome pattern across the various genomes has an interesting one-to-one correspondence with the CpG dinucleotide distribution density in the genome and with gene density (Figure 4).

Bottom Line: Furthermore, they are inversely correlated with the H3K9Ac landscape and gene expression as measured in MCF-7 cells.Treatment with drugs resulted in en-bloc changes to the methylation domains.Taken together these results suggest that the human genome is organized in epigenomic domains that contain various different types of genes and imply that there are cis- and trans-regulators that control these domain-wide epigenetic changes and hence gene expression in the human genome.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Biology and Biochemistry, National Yang Ming University, No.155, Sec.2, Linong Street, Taipei, 112 Taiwan. mth@ym.edu.tw.

ABSTRACT
We have previously identified large megabase-sized hypomethylated zones in the genome of the breast cancer cell line MCF-7 using the TspRI-ExoIII technique. In this report, we used a more convenient high throughput method for mapping the hypomethylated zones in a number of human tumor genomes simultaneously. The method was validated by the bisulfite sequencing of 39 randomly chosen sites in a demethylated domain and by bisulfite genome-wide sequencing of the MCF-7 genome. This showed that the genomes of the various tumor cell lines, as well as some primary tumors, exhibit common hypomethylated domains. Interestingly, these hypomethylated domains are correlated with low CpG density distribution genome-wide, together with the histone H3K27Me3 landscape. Furthermore, they are inversely correlated with the H3K9Ac landscape and gene expression as measured in MCF-7 cells. Treatment with drugs resulted in en-bloc changes to the methylation domains. A close examination of the methylation domains found differences between non-invasive and invasive tumors with respect to tumorigenesis related genes. Taken together these results suggest that the human genome is organized in epigenomic domains that contain various different types of genes and imply that there are cis- and trans-regulators that control these domain-wide epigenetic changes and hence gene expression in the human genome. The hypomethylated domains are located in gene deserts that contain mainly tissue-specific genes and therefore we hypothesize that tumor cells keep these regions demethylated and silenced in order to save energy and resources and allow higher levels of cell proliferation and better survival (a thrifty tumor genome hypothesis).

No MeSH data available.


Related in: MedlinePlus