Open Access Highly Accessed Research article

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

Ping Liang1*, Fei Song23, Srimoyee Ghosh45, Evan Morien46, Maochun Qin4, Saleh Mahmood27, Kyoko Fujiwara48, Jun Igarashi8, Hiroki Nagase489* and William A Held2

Author Affiliations

1 Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada

2 Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY, USA

3 Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA

4 Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA

5 Department of Zoology, North-Eastern Hill University, Umshing Mawkynroh, Shillong, Meghalaya, India

6 Department of Bioinformatics, University of British Columbia, Vancouver, British Columbia, Canada

7 Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY, USA

8 Division of Cancer Genetics, Department of Advanced Medical Science, Nihon University School of Medicine, Tokyo, Japan

9 Division of Cancer Genetics, Chiba Cancer Center, Research Institute, Chiba, Japan

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BMC Genomics 2011, 12:231  doi:10.1186/1471-2164-12-231

Published: 11 May 2011

Additional files

Additional file 1:

E15 and ES T-DMRs.

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Additional file 2:

MeDIP/NimbleGen Promoter + CpGi Array (Tiling region): Methylation analysis of KvDMR region. The scaled log2 ratio of the 40 Kb region on chromosome 7 near KvDMR is shown. The numbers on the top indicate the genomic position. The rectangle indicates the position of the KvDMR that includes two CpGi regions. Two independent tissues were taken from different mice. Previous studies indicate that the KvDMR is methylated in somatic tissue and unmethylated in sperm [57].

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Additional file 3:

T-DMRs in tiling regions.

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Additional file 4:

Pearson Coefficient and common peak number between replicates.

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Additional file 5:

a: Overlaps between different tissues for DS-DMRs with testis excluded; b:Overlaps between tissues for DMRs shared by all developmental stages in a tissue.

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Additional file 6:

T-DMRs within the Hoxa gene cluster. The MeDIP methylation profile for the Hoxa gene cluster within the 52.08 to 52.20 Mb region on chromosome 6 is shown. The locations of CpGi regions, Hoxa gene transcripts from a1 to a13 and transcription direction are indicated. The numbers on the bottom from 1 to 8 indicate the position of methylation peaks (represented by the log2 ratio) corresponding to those listed in Additional file 7.

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Additional file 7:

Methylation peaks locations in the Hoxa gene cluster.

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Additional file 8:

DNA methylation and alternative promoters for Pcdha genes. Methylation profile for Pcdha genes is shown in a similar manner as in Additional file 2. See also Additional file 9.

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Additional file 9:

Methylation peaks locations in the Protocadherin gene cluster.

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Additional file 10:

Relationship between T-DMRs and expression of their associated genes. The expression of the genes associated with liver unique T-DMRs were compared to that of the same gene set in the three other tissues broken down into the CpGi promoter (CpGi_P), non-CpGi promoter (NCpGi_P) and intra-genic CpGi (Intra_CpGi) groups using boxplots (panel A, B and C, respectively). Comparison was also made for T-DMRs associated genes across different location groups within liver (Panel D). The p values of pairwise t-tests between liver and each of the other tissue (panels A-C) and between each pair of location groups (panel C) are provided on the right side of the boxplots with those no great than 0.05 shown in bold font. "NDMR" in panel C refers to genes associated with all genes not associated with liver unique T-DMRs.

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Additional file 11:

Gene ontology for T-DMRs in adult.

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Additional file 12:

Gene ontology for DS-DMRs subjected to methylation or demethylation in adult.

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Additional file 13:

A list of Sequenom MassARRAY primers used for Validation.

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Additional file 14:

Scatter plots of log2 ratios of two replicates for brain tissues at E15, NB, and AD stages. Log2 ratio of all probes for the two replicate samples of brain at all stages were plotted. In each plot, data points in red rectangular area are those showing log2 ratio ≥ 1 (i.e. ratio ≥2) in both samples. Pearson Coefficient and the common methylation peak number are provided on the top of each plot.

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Additional file 15:

MeDIP/NimbleGen Promoter + CpGi Array: Methylation analysis of RLGS T-DMR loci. The MeDIP methylation profile including scaled log2 ratio and methylation peaks of four RLGS T-DMR loci are shown (Pst4, Pst10, Pvu4 and Pvu5). The loci were identified as T-DMRs by RLGS [32]. The CpG island, genomic location, relevant gene and the direction of each transcript are indicated. The log2 ratio is the ratio of signals for the input and immunoprecipitated DNA test samples that were co-hybridized to the array. RLGS T-DMRs were also confirmed by Sequenom MassARRAY ([32], and data not shown).

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Additional file 16:

Comparison of methylation data between MeDIP/NimbleGen Promoter + CpGi Array and Sequenom MassARRAY: Non CpGi promoter region (randomly selected). Data similar to that presented in Figure 1 for a randomly selected locus, the non-CpGi promoter region of Gm1070 that is methylated in liver and ES, but not in testis.

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Additional file 17:

MeDIP/NimbleGen Promoter + CpGi Array (Tiling region): Methylation analysis of Igf2r imprint control region. The MeDIP methylation profile of a region on chromosome 17 that includes Igf2r and BC009123 is shown. The numbers on the top indicate the genomic position. The CpGi in the rectangle is located close to the promoter region of BC009123 and the second intron of Igf2r. Methylation within the CpGi is associated with repression of transcription of Airn antisense RNA located somewhat downstream of TSS for BC009123. The imprinting control region (rectangle) is monoallelically methylated in somatic tissue and unmethylated in testis [57].

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