title: Genome-wide quantitative assessment of variation in DNA methylation patterns.
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.
authors.affiliation: Falk Brain Tumor Center, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago IL 60614-3394, USA. hxie@childrensmemorial.org
authors.forename: Hehuang
authors.initials: H
authors.lastname: Xie
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Alexandre
authors.initials: A
authors.lastname: de Andrade
authors.forename: Maria de F
authors.initials: Mde F
authors.lastname: Bonaldo
authors.forename: Vasil
authors.initials: V
authors.lastname: Galat
authors.forename: Kelly
authors.initials: K
authors.lastname: Arndt
authors.forename: Veena
authors.initials: V
authors.lastname: Rajaram
authors.forename: Stewart
authors.initials: S
authors.lastname: Goldman
authors.forename: Tadanori
authors.initials: T
authors.lastname: Tomita
authors.forename: Marcelo B
authors.initials: MB
authors.lastname: Soares
mesh_terms: D000483:Alleles; D020087:Alu Elements; D002460:Cell Line; D002891:Chromosomes, Human, Pair 21; D018899:CpG Islands; D019175:DNA Methylation; D003627:Data Interpretation, Statistical; D019277:Entropy; D044127:Epigenesis, Genetic; D015894:Genome, Human; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D011401:Promoter Regions, Genetic