Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, Principado de Asturias, Spain.
Fundación para la Investigación Biosanitaria de Asturias (FINBA), Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Principado de Asturias, Spain.
Epigenomics. 2018 Jul;10(7):903-923. doi: 10.2217/epi-2017-0163. Epub 2018 Apr 5.
Epigenetic regulation plays an important role in cellular development and differentiation. A detailed map of the DNA methylation dynamics that occur during cell differentiation would contribute to decipher the molecular networks governing cell fate commitment.
Illumina MethylationEPIC BeadChip platform was used to describe the genome-wide DNA methylation changes observed throughout hematopoietic maturation by analyzing multiple myeloid and lymphoid hematopoietic cell types.
We identified a plethora of DNA methylation changes that occur during human hematopoietic differentiation. We observed that T lymphocytes display substantial enhancement of de novo CpG hypermethylation as compared with other hematopoietic cell populations. T-cell-specific hypermethylated regions were strongly associated with open chromatin marks and enhancer elements, as well as binding sites of specific key transcription factors involved in hematopoietic differentiation, such as PU.1 and TAL1.
These results provide novel insights into the role of DNA methylation at enhancer elements in T-cell development.
表观遗传调控在细胞发育和分化中起着重要作用。细胞分化过程中发生的 DNA 甲基化动态的详细图谱将有助于解析调控细胞命运决定的分子网络。
通过分析多种髓系和淋巴造血细胞类型，我们使用 Illumina MethylationEPIC BeadChip 平台描述了造血成熟过程中观察到的全基因组 DNA 甲基化变化。
我们鉴定出在人类造血分化过程中发生的大量 DNA 甲基化变化。与其他造血细胞群体相比，我们观察到 T 淋巴细胞表现出大量新生成的 CpG 超甲基化。T 细胞特异性高甲基化区域与开放染色质标记和增强子元件以及参与造血分化的特定关键转录因子（如 PU.1 和 TAL1）的结合位点强烈相关。
这些结果为增强子元件中的 DNA 甲基化在 T 细胞发育中的作用提供了新的见解。
