Epigenome-wide analysis reveals specific DNA hypermethylation of T cells during human hematopoietic differentiation

Abstract

Aim: 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. Methods: 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. Results: 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. Conclusion: These results provide novel insights into the role of DNA methylation at enhancer elements in T-cell development.