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Your search keyword '"Vlaming, Hanneke"' showing total 3 results
Start Over Author "Vlaming, Hanneke" Journal proceedings of the national academy of sciences of the united states of america
3 results on '"Vlaming, Hanneke"'

2. The histone methyltransferase DOT1L prevents antigen-independent differentiation and safeguards epigenetic identity of CD8+ T cells.

Author

Kwesi-Maliepaard, Eliza Mari, Aslam, Muhammad Assad, Alemdehy, Mir Farshid, den Brand, Teun van, McLean, Chelsea, Vlaming, Hanneke, Welsem, Tibor van, Korthout, Tessy, Lancini, Cesare, Hendriks, Sjoerd, Ahrends, Tomasz, Dinther, Dieke van, den Haan, Joke M. M., Borst, Jannie, Wit, Elzo de, Leeuwen, Fred van, and Jacobs, Heinz

Subjects
T cells, CYTOTOXIC T cells, T cell differentiation, T cell receptors, PHYSIOLOGY
Abstract

Cytotoxic T cell differentiation is guided by epigenome adaptations, but how epigenetic mechanisms control lymphocyte development has not been well defined. Here we show that the histone methyltransferase DOT1L, which marks the nucleosome core on active genes, safeguards normal differentiation of CD8+ T cells. T cell-specific ablation of Dot1L resulted in loss of naïve CD8+ T cells and premature differentiation toward a memory-like state, independent of antigen exposure and in a cell-intrinsic manner. Mechanistically, DOT1L controlled CD8+ T cell differentiation by ensuring normal T cell receptor density and signaling. DOT1L also maintained epigenetic identity, in part by indirectly supporting the repression of developmentally regulated genes. Finally, deletion of Dot1L in T cells resulted in an impaired immune response. Through our study, DOT1L is emerging as a central player in physiology of CD8+ T cells, acting as a barrier to prevent premature differentiation and controlling epigenetic integrity. [ABSTRACT FROM AUTHOR]

Published
2020
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3. The histone methyltransferase DOT1L prevents antigen-independent differentiation and safeguards epigenetic identity of CD8 + T cells.

Author

Kwesi-Maliepaard EM, Aslam MA, Alemdehy MF, van den Brand T, McLean C, Vlaming H, van Welsem T, Korthout T, Lancini C, Hendriks S, Ahrends T, van Dinther D, den Haan JMM, Borst J, de Wit E, van Leeuwen F, and Jacobs H

Subjects
Animals, Antigens, Differentiation genetics, Antigens, Differentiation metabolism, Cell Differentiation genetics, Epigenesis, Genetic genetics, Epigenomics, Female, Histone Methyltransferases metabolism, Histone-Lysine N-Methyltransferase physiology, Histones metabolism, Male, Methyltransferases metabolism, Mice, CD8-Positive T-Lymphocytes metabolism, Histone-Lysine N-Methyltransferase metabolism
Abstract

Cytotoxic T cell differentiation is guided by epigenome adaptations, but how epigenetic mechanisms control lymphocyte development has not been well defined. Here we show that the histone methyltransferase DOT1L, which marks the nucleosome core on active genes, safeguards normal differentiation of CD8 + T cells. T cell-specific ablation of Dot1L resulted in loss of naïve CD8 + T cells and premature differentiation toward a memory-like state, independent of antigen exposure and in a cell-intrinsic manner. Mechanistically, DOT1L controlled CD8 + T cell differentiation by ensuring normal T cell receptor density and signaling. DOT1L also maintained epigenetic identity, in part by indirectly supporting the repression of developmentally regulated genes. Finally, deletion of Dot1L in T cells resulted in an impaired immune response. Through our study, DOT1L is emerging as a central player in physiology of CD8 + T cells, acting as a barrier to prevent premature differentiation and controlling epigenetic integrity., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Published
2020
Full Text
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