Genome-wide quantitative assessment of variation in DNA methylation patterns
| Autor: | Stewart Goldman, Maria de Fatima Bonaldo, Min Wang, Alexandre de Andrade, Veena Rajaram, Marcelo B. Soares, Tadanori Tomita, Hehuang Xie, Kelly Arndt, Vasil Galat |
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| Rok vydání: | 2013 |
| Předmět: |
Chromosomes
Human Pair 21 Entropy Bisulfite sequencing Gene Regulation Chromatin and Epigenetics Biology Genome Cell Line Epigenesis Genetic Epigenetics of physical exercise Alu Elements Neoplasms Genetics Quantitative assessment Humans Promoter Regions Genetic RNA-Directed DNA Methylation Alleles Epigenomics Genome Human Methylation DNA Methylation Differentially methylated regions Variation (linguistics) Data Interpretation Statistical DNA methylation Nucleic acid Illumina Methylation Assay CpG Islands Corrigendum |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkt209 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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