Genome-wide quantitative assessment of variation in DNA methylation patterns

Hehuang Xie, Min Wang, Alexandre De Andrade, Maria De F Bonaldo, Vasil Galat, Kelly Arndt, Veena Rajaram, Stewart Goldman, Tadanori Tomita, Marcelo B. Soares

Research output: Contribution to journalArticle

44 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4099-4108
Number of pages10
JournalNucleic acids research
Volume39
Issue number10
DOIs
StatePublished - May 2011

ASJC Scopus subject areas

  • Genetics

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    Xie, H., Wang, M., De Andrade, A., Bonaldo, M. D. F., Galat, V., Arndt, K., Rajaram, V., Goldman, S., Tomita, T., & Soares, M. B. (2011). Genome-wide quantitative assessment of variation in DNA methylation patterns. Nucleic acids research, 39(10), 4099-4108. https://doi.org/10.1093/nar/gkr017