Using high-resolution molecular and optical mapping of the three-dimensional genome, we found that the transcription factor TCF-1 is linked to changes in the structure of topologically associating domains in T cell progenitors that lead to interactions between previously insulated regulatory elements and target genes at late stages of T cell development.
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References
Verbeek, S. et al. An HMG-box-containing T-cell factor required for thymocyte differentiation. Nature 374, 70–74 (1995). This was the first study to demonstrate that genetic deletion of Tcf7 leads to aberrant T cell development.
Johnson, J. L. et al. Lineage-determining transcription factor TCF-1 initiates the epigenetic identity of T cells. Immunity 48, 243–257.e10 (2018). This study demonstrated the ability of TCF-1 to bind nucleosomes and create accessible chromatin in fibroblasts and T cells.
Emmanuel, A. O. et al. TCF-1 and HEB cooperate to establish the epigenetic and transcription profiles of CD4+ CD8+ thymocytes. Nat. Immunol. 19, 1366–1378 (2018). This study revealed that the transcriptional regulatory protein HEB cooperates with TCF-1 to create the accessible landscape of thymocytes.
Giese, K., Cox, J. & Grosschedl, R. The HMG domain of lymphoid enhancer factor 1 bends DNA and facilitates assembly of functional nucleoprotein structures. Cell 69, 185–195 (1992). This was the first study to show that the HMG domain of the transcription factor LEF1 induces a bend of ~130° in the DNA helix.
Hu, G. et al. Transformation of accessible chromatin and 3D nucleome underlies lineage commitment of early T cells. Immunity 20, 227–242.e8 (2018). This was the first comprehensive atlas of 3D genome folding in thymocytes at various developmental stages.
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This is a summary of: Wang, W. et al. TCF-1 promotes chromatin interactions across topologically associating domains in T cell progenitors. Nat. Immunol. https://doi.org/10.1038//s41590-022-01232-z (2022).
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TCF-1 mediates chromatin intermingling during T cell development. Nat Immunol 23, 1000–1001 (2022). https://doi.org/10.1038/s41590-022-01237-8
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DOI: https://doi.org/10.1038/s41590-022-01237-8
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