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

BMC Genomics

Research Article

Ping Liang¹  Maochun Qin²  Evan Morien³  Srimoyee Ghosh⁴  Kyoko Fujiwara⁵  Hiroki Nagase⁶  William A Held⁷  Saleh Mahmood⁸  Fei Song⁹  Jun Igarashi^1,10 

[1] Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada;Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA;Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA;Department of Bioinformatics, University of British Columbia, Vancouver, British Columbia, Canada;Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA;Department of Zoology, North-Eastern Hill University, Umshing Mawkynroh, Shillong, Meghalaya, India;Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA;Division of Cancer Genetics, Department of Advanced Medical Science, Nihon University School of Medicine, Tokyo, Japan;Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA;Division of Cancer Genetics, Department of Advanced Medical Science, Nihon University School of Medicine, Tokyo, Japan;Division of Cancer Genetics, Chiba Cancer Center, Research Institute, Chiba, Japan;Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY, USA;Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY, USA;Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY, USA;Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY, USA;Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA;Division of Cancer Genetics, Department of Advanced Medical Science, Nihon University School of Medicine, Tokyo, Japan;

关键词: Alternative Promoter;    Tiling Array;    Methylation Difference;    Gene Body Methylation;    Methylation Peak;   

DOI  :  10.1186/1471-2164-12-231

 received in 2010-06-25, accepted in 2011-05-11,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundChanges 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.ResultsIn this study Me thylated D NA I mmunoP recipitation (MeDIP) was used in conjunction with a NimbleGen promoter plus CpG island (CpGi) array to identify T issue and D evelopmental S tage specific D ifferentially M ethylated DNA R egions (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).ConclusionsOur 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.

【 授权许可】

CC BY   
© Liang et al; licensee BioMed Central Ltd. 2011