TY - JOUR
T1 - Genome-wide quantitative assessment of variation in DNA methylation patterns
AU - Xie, Hehuang
AU - Wang, Min
AU - De Andrade, Alexandre
AU - Bonaldo, Maria De F.
AU - Galat, Vasil
AU - Arndt, Kelly
AU - Rajaram, Veena
AU - Goldman, Stewart
AU - Tomita, Tadanori
AU - Soares, Marcelo B.
N1 - Funding Information:
Funding for open access charge: NHLBI10279457; Everett/O’Connor Charitable Trust; Dr Ralph and Marian C. Falk Medical Research Trust; Gus Foundation; Maeve McNicholas Memorial Foundation and Medical Research Institute Council.
PY - 2011/5
Y1 - 2011/5
N2 - 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.
AB - 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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U2 - 10.1093/nar/gkr017
DO - 10.1093/nar/gkr017
M3 - Article
C2 - 21278160
AN - SCOPUS:79961177841
SN - 0305-1048
VL - 39
SP - 4099
EP - 4108
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 10
ER -