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

42 Citations (Scopus)

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

Fingerprint

DNA Methylation
Entropy
Methylation
Genome
Alu Elements
Population
CpG Islands
Base Composition
Fibroblasts
Maintenance
Neoplasms

ASJC Scopus subject areas

  • Genetics

Cite this

Xie, H., Wang, M., De Andrade, A., Bonaldo, M. D. F., Galat, V., Arndt, K., ... 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

Genome-wide quantitative assessment of variation in DNA methylation patterns. / Xie, Hehuang; Wang, Min; De Andrade, Alexandre; Bonaldo, Maria De F; Galat, Vasil; Arndt, Kelly; Rajaram, Veena; Goldman, Stewart; Tomita, Tadanori; Soares, Marcelo B.

In: Nucleic Acids Research, Vol. 39, No. 10, 05.2011, p. 4099-4108.

Research output: Contribution to journalArticle

Xie, H, Wang, M, De Andrade, A, Bonaldo, MDF, Galat, V, Arndt, K, Rajaram, V, Goldman, S, Tomita, T & Soares, MB 2011, 'Genome-wide quantitative assessment of variation in DNA methylation patterns', Nucleic Acids Research, vol. 39, no. 10, pp. 4099-4108. https://doi.org/10.1093/nar/gkr017
Xie H, Wang M, De Andrade A, Bonaldo MDF, Galat V, Arndt K et al. Genome-wide quantitative assessment of variation in DNA methylation patterns. Nucleic Acids Research. 2011 May;39(10):4099-4108. https://doi.org/10.1093/nar/gkr017
Xie, Hehuang ; Wang, Min ; De Andrade, Alexandre ; Bonaldo, Maria De F ; Galat, Vasil ; Arndt, Kelly ; Rajaram, Veena ; Goldman, Stewart ; Tomita, Tadanori ; Soares, Marcelo B. / Genome-wide quantitative assessment of variation in DNA methylation patterns. In: Nucleic Acids Research. 2011 ; Vol. 39, No. 10. pp. 4099-4108.
@article{34398b7abb8a4419abf65982254f94ef,
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.",
author = "Hehuang Xie and Min Wang and {De Andrade}, Alexandre and Bonaldo, {Maria De F} and Vasil Galat and Kelly Arndt and Veena Rajaram and Stewart Goldman and Tadanori Tomita and Soares, {Marcelo B.}",
year = "2011",
month = "5",
doi = "10.1093/nar/gkr017",
language = "English (US)",
volume = "39",
pages = "4099--4108",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "10",

}

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=79961177841&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79961177841&partnerID=8YFLogxK

U2 - 10.1093/nar/gkr017

DO - 10.1093/nar/gkr017

M3 - Article

VL - 39

SP - 4099

EP - 4108

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 10

ER -