High-resolution genome-wide DNA methylation maps of mouse primary female dermal fibroblasts and keratinocytes

Epigenetics & Chromatin

Charles Vinson⁴  Andrew Smith²  Peter FitzGerald¹  Di Huang⁵  Ximiao He⁴  Raghunath Chatterjee³ 

[1] Genome Analysis Unit, Genetics Branch, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA;Molecular and Computational Biology, University of Southern California, 1050 Childs Way, Los Angeles, CA 90089, USA;Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata 700108, India;Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA;NCBI, National Institutes of Health, 8600 Rockville Pike, Bethesda, MD 20894, USA

关键词: Fibroblasts;    Keratinocytes;    C/EBPβ;    CTCF;    Methylome;    HMR;    Hypomethylated regions;    CG methylation;   

Others  :  1123306
DOI  :  10.1186/1756-8935-7-35

 received in 2014-08-06, accepted in 2014-11-04,  发布年份 2014

【 摘 要 】

Background

Genome-wide DNA methylation at a single nucleotide resolution in different primary cells of the mammalian genome helps to determine the characteristics and functions of tissue-specific hypomethylated regions (TS-HMRs). We determined genome-wide cytosine methylation maps at 91X and 36X coverage of newborn female mouse primary dermal fibroblasts and keratinocytes and compared with mRNA-seq gene expression data.

Results

These high coverage methylation maps were used to identify HMRs in both cell types. A total of 2.91% of the genome are in keratinocyte HMRs, and 2.15% of the genome are in fibroblast HMRs with 1.75% being common. Half of the TS-HMRs are extensions of common HMRs, and the remaining are unique TS-HMRs. Four levels of CG methylation are observed: 1) total unmethylation for CG dinucleotides in HMRs in CGIs that are active in all tissues; 2) 10% to 40% methylation for TS-HMRs; 3) 60% methylation for TS-HMRs in cells types where they are not in HMRs; and 4) 70% methylation for the nonfunctioning part of the genome. SINE elements are depleted inside the TS-HMRs, while highly enriched in the surrounding regions. Hypomethylation at the last exon shows gene repression, while demethylation toward the gene body positively correlates with gene expression. The overlapping HMRs have a more complex relationship with gene expression. The common HMRs and TS-HMRs are each enriched for distinct Transcription Factor Binding Sites (TFBS). C/EBPβ binds to methylated regions outside of HMRs while CTCF prefers to bind in HMRs, highlighting these two parts of the genome and their potential interactions.

Conclusions

Keratinocytes and fibroblasts are of epithelial and mesenchymal origin. High-resolution methylation maps in these two cell types can be used as reference methylomes for analyzing epigenetic mechanisms in several diseases including cancer.

Please see related article at the following link: http://www.epigeneticsandchromatin.com/content/7/1/34 webcite

【 授权许可】

   
2014 Chatterjee et al.; licensee BioMed Central Ltd.

【 图 表 】

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