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Genome-wide quantitative assessment of variation in DNA methylation patterns.

Xie H, Wang M, de Andrade A, Bonaldo Mde F, Galat V, Arndt K, Rajaram V, Goldman S, Tomita T, Soares MB - Nucleic Acids Res. (2011)

Bottom Line: However, little is known about genome-wide variation of DNA methylation patterns.We further identified 12 putative allelic-specific methylated genomic loci, including four Alu elements and eight promoters.Lastly, using subcloned normal fibroblast cells, we demonstrated the highly variable methylation patterns are resulted from low fidelity of DNA methylation inheritance.

View Article: PubMed Central - PubMed

Affiliation: Falk Brain Tumor Center, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago IL 60614-3394, USA. hxie@childrensmemorial.org

ABSTRACT
Genomic DNA methylation contributes substantively to transcriptional regulations that underlie mammalian development and cellular differentiation. Much effort has been made to decipher the molecular mechanisms governing the establishment and maintenance of DNA methylation patterns. However, little is known about genome-wide variation of DNA methylation patterns. In this study, we introduced the concept of methylation entropy, a measure of the randomness of DNA methylation patterns in a cell population, and exploited it to assess the variability in DNA methylation patterns of Alu repeats and promoters. A few interesting observations were made: (i) within a cell population, methylation entropy varies among genomic loci; (ii) among cell populations, the methylation entropies of most genomic loci remain constant; (iii) compared to normal tissue controls, some tumors exhibit greater methylation entropies; (iv) Alu elements with high methylation entropy are associated with high GC content but depletion of CpG dinucleotides and (v) Alu elements in the intronic regions or far from CpG islands are associated with low methylation entropy. We further identified 12 putative allelic-specific methylated genomic loci, including four Alu elements and eight promoters. Lastly, using subcloned normal fibroblast cells, we demonstrated the highly variable methylation patterns are resulted from low fidelity of DNA methylation inheritance.

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The correlation of methylation entropies between the primary and relapsed ependymoma tissues from one individual. Each dot represents a genomic locus with the methylation entropies calculated for primary (PA1*) and relapsed (RL1*) tumors.
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Figure 4: The correlation of methylation entropies between the primary and relapsed ependymoma tissues from one individual. Each dot represents a genomic locus with the methylation entropies calculated for primary (PA1*) and relapsed (RL1*) tumors.

Mentions: We further focused our analysis on the methylation entropies of genomic loci for which there were 16 or more sequence-reads in at least two samples. All possible pairwise comparisons were performed with the eight tissue samples to uncover differences in the methylation entropies of these genomic loci. Interestingly, we found that methylation entropies of most genomic loci remained constant regardless of the tissue source. To demonstrate such constancy, we determined the Pearson’s correlation of methylation entropies for all pairwise comparisons. Modest corrections (ranging from 0.29 to 0.65) were identified with an average of 0.5 for a given pair (Supplementary Table S1A). In particular, the most significant correlation was observed for the methylation entropies of 935 loci from a primary aggressive and a recurrent ependymoma derived from the same individual (Figure 4). Altogether, these results indicated that for a given locus and tissue, methylation entropies can be similar among individuals. On the other hand, it also suggested that the observed variation in DNA methylation pattern is locus specific.Figure 4.


Genome-wide quantitative assessment of variation in DNA methylation patterns.

Xie H, Wang M, de Andrade A, Bonaldo Mde F, Galat V, Arndt K, Rajaram V, Goldman S, Tomita T, Soares MB - Nucleic Acids Res. (2011)

The correlation of methylation entropies between the primary and relapsed ependymoma tissues from one individual. Each dot represents a genomic locus with the methylation entropies calculated for primary (PA1*) and relapsed (RL1*) tumors.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3105398&req=5

Figure 4: The correlation of methylation entropies between the primary and relapsed ependymoma tissues from one individual. Each dot represents a genomic locus with the methylation entropies calculated for primary (PA1*) and relapsed (RL1*) tumors.
Mentions: We further focused our analysis on the methylation entropies of genomic loci for which there were 16 or more sequence-reads in at least two samples. All possible pairwise comparisons were performed with the eight tissue samples to uncover differences in the methylation entropies of these genomic loci. Interestingly, we found that methylation entropies of most genomic loci remained constant regardless of the tissue source. To demonstrate such constancy, we determined the Pearson’s correlation of methylation entropies for all pairwise comparisons. Modest corrections (ranging from 0.29 to 0.65) were identified with an average of 0.5 for a given pair (Supplementary Table S1A). In particular, the most significant correlation was observed for the methylation entropies of 935 loci from a primary aggressive and a recurrent ependymoma derived from the same individual (Figure 4). Altogether, these results indicated that for a given locus and tissue, methylation entropies can be similar among individuals. On the other hand, it also suggested that the observed variation in DNA methylation pattern is locus specific.Figure 4.

Bottom Line: However, little is known about genome-wide variation of DNA methylation patterns.We further identified 12 putative allelic-specific methylated genomic loci, including four Alu elements and eight promoters.Lastly, using subcloned normal fibroblast cells, we demonstrated the highly variable methylation patterns are resulted from low fidelity of DNA methylation inheritance.

View Article: PubMed Central - PubMed

Affiliation: Falk Brain Tumor Center, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago IL 60614-3394, USA. hxie@childrensmemorial.org

ABSTRACT
Genomic DNA methylation contributes substantively to transcriptional regulations that underlie mammalian development and cellular differentiation. Much effort has been made to decipher the molecular mechanisms governing the establishment and maintenance of DNA methylation patterns. However, little is known about genome-wide variation of DNA methylation patterns. In this study, we introduced the concept of methylation entropy, a measure of the randomness of DNA methylation patterns in a cell population, and exploited it to assess the variability in DNA methylation patterns of Alu repeats and promoters. A few interesting observations were made: (i) within a cell population, methylation entropy varies among genomic loci; (ii) among cell populations, the methylation entropies of most genomic loci remain constant; (iii) compared to normal tissue controls, some tumors exhibit greater methylation entropies; (iv) Alu elements with high methylation entropy are associated with high GC content but depletion of CpG dinucleotides and (v) Alu elements in the intronic regions or far from CpG islands are associated with low methylation entropy. We further identified 12 putative allelic-specific methylated genomic loci, including four Alu elements and eight promoters. Lastly, using subcloned normal fibroblast cells, we demonstrated the highly variable methylation patterns are resulted from low fidelity of DNA methylation inheritance.

Show MeSH
Related in: MedlinePlus