title: High-resolution genome-wide DNA methylation maps of mouse primary female dermal fibroblasts and keratinocytes.
abstract: 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.
authors.affiliation: Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892 USA.|Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata, 700108 India.
authors.forename: Raghunath
authors.initials: R
authors.lastname: Chatterjee
authors.affiliation: Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892 USA.
authors.forename: Ximiao
authors.initials: X
authors.lastname: He
authors.affiliation: NCBI, National Institutes of Health, 8600 Rockville Pike, Bethesda, MD 20894 USA.
authors.forename: Di
authors.initials: D
authors.lastname: Huang
authors.affiliation: Genome Analysis Unit, Genetics Branch, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892 USA.
authors.forename: Peter
authors.initials: P
authors.lastname: FitzGerald
authors.affiliation: Molecular and Computational Biology, University of Southern California, 1050 Childs Way, Los Angeles, CA 90089 USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Smith
authors.affiliation: Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892 USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Vinson
keywords: C/EBPβ; CG methylation; CTCF; Fibroblasts; HMR; Hypomethylated regions; Keratinocytes; Methylome