Genome-wide survey reveals dynamic widespread tissue-specific changes in DNA methylation during development

<p>Abstract</p> <p>Background</p> <p>Changes in DNA methylation in the mammalian genome during development are frequent events and play major roles regulating gene expression and other developmental processes. It is necessary to identify these events so that we may unde...

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Main Authors: Mahmood Saleh, Qin Maochun, Morien Evan, Ghosh Srimoyee, Song Fei, Liang Ping, Fujiwara Kyoko, Igarashi Jun, Nagase Hiroki, Held William A
Format: Article
Language:English
Published: BMC 2011-05-01
Series:BMC Genomics
Online Access:http://www.biomedcentral.com/1471-2164/12/231
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spelling doaj-89b47ac3849544ce9ea6eb496fde15292020-11-24T20:51:48ZengBMCBMC Genomics1471-21642011-05-0112123110.1186/1471-2164-12-231Genome-wide survey reveals dynamic widespread tissue-specific changes in DNA methylation during developmentMahmood SalehQin MaochunMorien EvanGhosh SrimoyeeSong FeiLiang PingFujiwara KyokoIgarashi JunNagase HirokiHeld William A<p>Abstract</p> <p>Background</p> <p>Changes in DNA methylation in the mammalian genome during development are frequent events and play major roles regulating gene expression and other developmental processes. It is necessary to identify these events so that we may understand how these changes affect normal development and how aberrant changes may impact disease.</p> <p>Results</p> <p>In this study Methylated DNA ImmunoPrecipitation (MeDIP) was used in conjunction with a NimbleGen promoter plus CpG island (CpGi) array to identify Tissue and Developmental Stage specific Differentially Methylated DNA Regions (T-DMRs and DS-DMRs) on a genome-wide basis. Four tissues (brain, heart, liver, and testis) from C57BL/6J mice were analyzed at three developmental stages (15 day embryo, E15; new born, NB; 12 week adult, AD). Almost 5,000 adult T-DMRs and 10,000 DS-DMRs were identified. Surprisingly, almost all DS-DMRs were tissue specific (i.e. methylated in at least one tissue and unmethylated in one or more tissues). In addition our results indicate that many DS-DMRs are methylated at early development stages (E15 and NB) but are unmethylated in adult. There is a very strong bias for testis specific methylation in non-CpGi promoter regions (94%). Although the majority of T-DMRs and DS-DMRs tended to be in non-CpGi promoter regions, a relatively large number were also located in CpGi in promoter, intragenic and intergenic regions (>15% of the 15,979 CpGi on the array).</p> <p>Conclusions</p> <p>Our data suggests the vast majority of unique sequence DNA methylation has tissue specificity, that demethylation has a prominent role in tissue differentiation, and that DNA methylation has regulatory roles in alternative promoter selection and in non-promoter regions. Overall, our studies indicate changes in DNA methylation during development are a dynamic, widespread, and tissue-specific process involving both DNA methylation and demethylation.</p> http://www.biomedcentral.com/1471-2164/12/231
collection DOAJ
language English
format Article
sources DOAJ
author Mahmood Saleh
Qin Maochun
Morien Evan
Ghosh Srimoyee
Song Fei
Liang Ping
Fujiwara Kyoko
Igarashi Jun
Nagase Hiroki
Held William A
spellingShingle Mahmood Saleh
Qin Maochun
Morien Evan
Ghosh Srimoyee
Song Fei
Liang Ping
Fujiwara Kyoko
Igarashi Jun
Nagase Hiroki
Held William A
Genome-wide survey reveals dynamic widespread tissue-specific changes in DNA methylation during development
BMC Genomics
author_facet Mahmood Saleh
Qin Maochun
Morien Evan
Ghosh Srimoyee
Song Fei
Liang Ping
Fujiwara Kyoko
Igarashi Jun
Nagase Hiroki
Held William A
author_sort Mahmood Saleh
title Genome-wide survey reveals dynamic widespread tissue-specific changes in DNA methylation during development
title_short Genome-wide survey reveals dynamic widespread tissue-specific changes in DNA methylation during development
title_full Genome-wide survey reveals dynamic widespread tissue-specific changes in DNA methylation during development
title_fullStr Genome-wide survey reveals dynamic widespread tissue-specific changes in DNA methylation during development
title_full_unstemmed Genome-wide survey reveals dynamic widespread tissue-specific changes in DNA methylation during development
title_sort genome-wide survey reveals dynamic widespread tissue-specific changes in dna methylation during development
publisher BMC
series BMC Genomics
issn 1471-2164
publishDate 2011-05-01
description <p>Abstract</p> <p>Background</p> <p>Changes in DNA methylation in the mammalian genome during development are frequent events and play major roles regulating gene expression and other developmental processes. It is necessary to identify these events so that we may understand how these changes affect normal development and how aberrant changes may impact disease.</p> <p>Results</p> <p>In this study Methylated DNA ImmunoPrecipitation (MeDIP) was used in conjunction with a NimbleGen promoter plus CpG island (CpGi) array to identify Tissue and Developmental Stage specific Differentially Methylated DNA Regions (T-DMRs and DS-DMRs) on a genome-wide basis. Four tissues (brain, heart, liver, and testis) from C57BL/6J mice were analyzed at three developmental stages (15 day embryo, E15; new born, NB; 12 week adult, AD). Almost 5,000 adult T-DMRs and 10,000 DS-DMRs were identified. Surprisingly, almost all DS-DMRs were tissue specific (i.e. methylated in at least one tissue and unmethylated in one or more tissues). In addition our results indicate that many DS-DMRs are methylated at early development stages (E15 and NB) but are unmethylated in adult. There is a very strong bias for testis specific methylation in non-CpGi promoter regions (94%). Although the majority of T-DMRs and DS-DMRs tended to be in non-CpGi promoter regions, a relatively large number were also located in CpGi in promoter, intragenic and intergenic regions (>15% of the 15,979 CpGi on the array).</p> <p>Conclusions</p> <p>Our data suggests the vast majority of unique sequence DNA methylation has tissue specificity, that demethylation has a prominent role in tissue differentiation, and that DNA methylation has regulatory roles in alternative promoter selection and in non-promoter regions. Overall, our studies indicate changes in DNA methylation during development are a dynamic, widespread, and tissue-specific process involving both DNA methylation and demethylation.</p>
url http://www.biomedcentral.com/1471-2164/12/231
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