Distinct and temporary-restricted epigenetic mechanisms regulate human αβ and γδ T cell development
Roels J, Kuchmiy A, De Decker M, et al.
The development of TCRαβ and TCRγδ T cells comprises a step-wise process in which regulatory events control differentiation and lineage outcome. To clarify these mechanisms, we employed RNA-sequencing, ATAC-sequencing and ChIPmentation on well-defined thymocyte subsets that represent the continuum of human T cell development. The chromatin accessibility dynamics show clear stage specificity and reveal that human T cell-lineage commitment is marked by GATA3- and BCL11B-dependent closing of PU.1 sites. A temporary increase in H3K27me3 without open chromatin modifications is unique for β-selection, whereas emerging γδ T cells, which originate from common precursors of β-selected cells, show large chromatin accessibility changes due to strong T cell receptor (TCR) signaling. Furthermore, we unravel distinct chromatin landscapes between CD4+ and CD8+ αβ-lineage cells that support their effector functions and reveal gene-specific mechanisms that define mature T cells. This resource provides a framework for studying gene regulatory mechanisms that drive normal and malignant human T cell development.
To ensure you see the information most relevant to you, please select your country.
Please note that your browser will need to be configured to accept cookies.
Diagenode will process your personal data in strict accordance with its privacy policy. This will include sending you updates about us, our products, and resources we think would be of interest to you.