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Putative Zinc Finger Protein Binding Sites Are Over-Represented in the Boundaries of Methylation-Resistant CpG Islands in the Human Genome

BACKGROUND: Majority of CpG dinucleotides in mammalian genomes tend to undergo DNA methylation, but most CpG islands are resistant to such epigenetic modification. Understanding about mechanisms that may lead to the methylation resistance of CpG islands is still very poor. METHODOLOGY/PRINCIPAL FIND...

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Detalles Bibliográficos
Autores principales: Fan, Shicai, Fang, Fang, Zhang, Xuegong, Zhang, Michael Q.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2065907/
https://www.ncbi.nlm.nih.gov/pubmed/18030324
http://dx.doi.org/10.1371/journal.pone.0001184
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author Fan, Shicai
Fang, Fang
Zhang, Xuegong
Zhang, Michael Q.
author_facet Fan, Shicai
Fang, Fang
Zhang, Xuegong
Zhang, Michael Q.
author_sort Fan, Shicai
collection PubMed
description BACKGROUND: Majority of CpG dinucleotides in mammalian genomes tend to undergo DNA methylation, but most CpG islands are resistant to such epigenetic modification. Understanding about mechanisms that may lead to the methylation resistance of CpG islands is still very poor. METHODOLOGY/PRINCIPAL FINDINGS: Using the genome-scale in vivo DNA methylation data from human brain, we investigated the flanking sequence features of methylation-resistant CpG islands, and discovered that there are several over-represented putative Transcription Factor Binding Sites (TFBSs) in methylation-resistant CpG islands, and a specific group of zinc finger protein binding sites are over-represented in boundary regions (∼400 bp) flanking such CpG islands. About 77% of the over-represented putative TFBSs are conserved among human, mouse and rat. We also observed the enrichment of 4 histone methylations in methylation-resistant CpG islands or their boundaries. CONCLUSIONS/SIGNIFICANCE: Our results suggest a possible mechanism that certain putative zinc finger protein binding sites over-represented in the boundary regions of the methylation-resistant CpG islands may block the spreading of methylation into these islands, and those TFBSs over-represented within the islands may both reinforce the methylation blocking and promote transcription. Some histone modifications may also enhance the immunity of the CpG islands against DNA methylation by augmenting these TFs' binding. We speculate that the dynamical equilibrium between methylation spreading and blocking is likely to be responsible for the establishment and maintenance of the relatively stable DNA methylation pattern in human somatic cells.
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spelling pubmed-20659072007-11-21 Putative Zinc Finger Protein Binding Sites Are Over-Represented in the Boundaries of Methylation-Resistant CpG Islands in the Human Genome Fan, Shicai Fang, Fang Zhang, Xuegong Zhang, Michael Q. PLoS One Research Article BACKGROUND: Majority of CpG dinucleotides in mammalian genomes tend to undergo DNA methylation, but most CpG islands are resistant to such epigenetic modification. Understanding about mechanisms that may lead to the methylation resistance of CpG islands is still very poor. METHODOLOGY/PRINCIPAL FINDINGS: Using the genome-scale in vivo DNA methylation data from human brain, we investigated the flanking sequence features of methylation-resistant CpG islands, and discovered that there are several over-represented putative Transcription Factor Binding Sites (TFBSs) in methylation-resistant CpG islands, and a specific group of zinc finger protein binding sites are over-represented in boundary regions (∼400 bp) flanking such CpG islands. About 77% of the over-represented putative TFBSs are conserved among human, mouse and rat. We also observed the enrichment of 4 histone methylations in methylation-resistant CpG islands or their boundaries. CONCLUSIONS/SIGNIFICANCE: Our results suggest a possible mechanism that certain putative zinc finger protein binding sites over-represented in the boundary regions of the methylation-resistant CpG islands may block the spreading of methylation into these islands, and those TFBSs over-represented within the islands may both reinforce the methylation blocking and promote transcription. Some histone modifications may also enhance the immunity of the CpG islands against DNA methylation by augmenting these TFs' binding. We speculate that the dynamical equilibrium between methylation spreading and blocking is likely to be responsible for the establishment and maintenance of the relatively stable DNA methylation pattern in human somatic cells. Public Library of Science 2007-11-21 /pmc/articles/PMC2065907/ /pubmed/18030324 http://dx.doi.org/10.1371/journal.pone.0001184 Text en Fan et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Fan, Shicai
Fang, Fang
Zhang, Xuegong
Zhang, Michael Q.
Putative Zinc Finger Protein Binding Sites Are Over-Represented in the Boundaries of Methylation-Resistant CpG Islands in the Human Genome
title Putative Zinc Finger Protein Binding Sites Are Over-Represented in the Boundaries of Methylation-Resistant CpG Islands in the Human Genome
title_full Putative Zinc Finger Protein Binding Sites Are Over-Represented in the Boundaries of Methylation-Resistant CpG Islands in the Human Genome
title_fullStr Putative Zinc Finger Protein Binding Sites Are Over-Represented in the Boundaries of Methylation-Resistant CpG Islands in the Human Genome
title_full_unstemmed Putative Zinc Finger Protein Binding Sites Are Over-Represented in the Boundaries of Methylation-Resistant CpG Islands in the Human Genome
title_short Putative Zinc Finger Protein Binding Sites Are Over-Represented in the Boundaries of Methylation-Resistant CpG Islands in the Human Genome
title_sort putative zinc finger protein binding sites are over-represented in the boundaries of methylation-resistant cpg islands in the human genome
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2065907/
https://www.ncbi.nlm.nih.gov/pubmed/18030324
http://dx.doi.org/10.1371/journal.pone.0001184
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