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Genome-wide quantitative assessment of variation in DNA methylation patterns

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 i...

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Autores principales: Xie, Hehuang, Wang, Min, de Andrade, Alexandre, de F. Bonaldo, Maria, Galat, Vasil, Arndt, Kelly, Rajaram, Veena, Goldman, Stewart, Tomita, Tadanori, Soares, Marcelo B.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105398/
https://www.ncbi.nlm.nih.gov/pubmed/21278160
http://dx.doi.org/10.1093/nar/gkr017
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author Xie, Hehuang
Wang, Min
de Andrade, Alexandre
de F. Bonaldo, Maria
Galat, Vasil
Arndt, Kelly
Rajaram, Veena
Goldman, Stewart
Tomita, Tadanori
Soares, Marcelo B.
author_facet Xie, Hehuang
Wang, Min
de Andrade, Alexandre
de F. Bonaldo, Maria
Galat, Vasil
Arndt, Kelly
Rajaram, Veena
Goldman, Stewart
Tomita, Tadanori
Soares, Marcelo B.
author_sort Xie, Hehuang
collection PubMed
description 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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spelling pubmed-31053982011-06-01 Genome-wide quantitative assessment of variation in DNA methylation patterns Xie, Hehuang Wang, Min de Andrade, Alexandre de F. Bonaldo, Maria Galat, Vasil Arndt, Kelly Rajaram, Veena Goldman, Stewart Tomita, Tadanori Soares, Marcelo B. Nucleic Acids Res Gene Regulation, Chromatin and Epigenetics 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. Oxford University Press 2011-05 2011-01-27 /pmc/articles/PMC3105398/ /pubmed/21278160 http://dx.doi.org/10.1093/nar/gkr017 Text en © The Author(s) 2011. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.5 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene Regulation, Chromatin and Epigenetics
Xie, Hehuang
Wang, Min
de Andrade, Alexandre
de F. Bonaldo, Maria
Galat, Vasil
Arndt, Kelly
Rajaram, Veena
Goldman, Stewart
Tomita, Tadanori
Soares, Marcelo B.
Genome-wide quantitative assessment of variation in DNA methylation patterns
title Genome-wide quantitative assessment of variation in DNA methylation patterns
title_full Genome-wide quantitative assessment of variation in DNA methylation patterns
title_fullStr Genome-wide quantitative assessment of variation in DNA methylation patterns
title_full_unstemmed Genome-wide quantitative assessment of variation in DNA methylation patterns
title_short Genome-wide quantitative assessment of variation in DNA methylation patterns
title_sort genome-wide quantitative assessment of variation in dna methylation patterns
topic Gene Regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105398/
https://www.ncbi.nlm.nih.gov/pubmed/21278160
http://dx.doi.org/10.1093/nar/gkr017
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