High-resolution genome-wide DNA methylation maps of mouse primary female dermal fibroblasts and keratinocytes
High-resolution genome-wide DNA methylation maps of mouse primary female dermal fibroblasts and keratinocytes
复制标题
DOI：
10.1186/1756-8935-7-35
复制
发表时间：
2014-12-02
影响因子：
3.9
通讯作者：
Vinson, Charles
中科院分区：
文献类型：
--
作者：
Chatterjee, Raghunath;He, Ximiao;Vinson, Charles
背景：哺乳动物基因组不同原代细胞中单核苷酸分辨率的全基因组 DNA 甲基化有助于确定组织特异性低甲基化区域 (TS-HMR) 的特征和功能。我们确定了新生雌性小鼠原代真皮成纤维细胞和角质形成细胞的全基因组胞嘧啶甲基化图谱，覆盖度为 91X 和 36X，并与 mRNA-seq 基因表达数据进行比较。结果：这些高覆盖度甲基化图谱用于识别两种细胞类型中的 HMR。总共 2.91% 的基因组位于角质形成细胞 HMR 中，2.15% 的基因组位于成纤维细胞 HMR 中，其中 1.75% 是常见的。一半的 TS-HMR 是常见 HMR 的扩展，其余的是独特的 TS-HMR。观察到四个水平的 CG 甲基化：1）在所有组织中活跃的 CGI 中 HMR 中 CG 二核苷酸的完全非甲基化； 2) TS-HMR 10% 至 40% 甲基化； 3) TS-HMR 在不属于 HMR 的细胞类型中 60% 甲基化； 4) 基因组无功能部分的 70% 甲基化。 SINE 元素在 TS-HMR 内部耗尽，而在周围区域高度富集。最后一个外显子的低甲基化表明基因受到抑制，而基因体的去甲基化则与基因表达呈正相关。重叠的 HMR 与基因表达有更复杂的关系。常见的 HMR 和 TS-HMR 均针对不同的转录因子结合位点 (TFBS) 进行了丰富。 C/EBP beta 与 HMR 之外的甲基化区域结合，而 CTCF 更喜欢在 HMR 中结合，突出了基因组的这两部分及其潜在的相互作用。结论：角质形成细胞和成纤维细胞具有上皮和间质来源。这两种细胞类型的高分辨率甲基化图谱可用作参考甲基化组，用于分析包括癌症在内的多种疾病的表观遗传机制。
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/EBP beta 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.