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

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About: The histone methyltransferase DOT1L prevents antigen-independent differentiation and safeguards epigenetic identity of CD8+ T cells Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	The histone methyltransferase DOT1L prevents antigen-independent differentiation and safeguards epigenetic identity of CD8+ T cells
Creator	Aslam, Muhammad Ahrends, Tomasz Borst, Jannie De Wit, Elzo Den Haan, Joke Farshid Alemdehy, Mir Hendriks, Sjoerd Jacobs, Heinz Korthout, Tessy Kwesi-Maliepaard, Eliza Lancini, Cesare Mclean, Chelsea Van Den Brand, Teun Van Dinther, Dieke Van Leeuwen, Fred Van Welsem, Tibor Vlaming, Hanneke
Source	BioRxiv
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 towards a memory-like state, independent of antigen exposure and in a cell-intrinsic manner. Without DOT1L, the memory-like CD8+ cells fail to acquire full effector functions in vitro and in vivo. Mechanistically, DOT1L controlled T-cell differentiation and function by ensuring normal T-cell receptor density and signaling, and by maintaining epigenetic identity, in part by indirectly supporting the repression of developmentally-regulated genes. 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 supporting the licensing of the full effector potential of cytotoxic T cells.
has issue date	2019-11-18(xsd:dateTime)
bibo:doi	10.1101/826255
has license	biorxiv
sha1sum (hex)	2f7564df663ecd0edf5d10113d70829e529d3116
schema:url	https://doi.org/10.1101/826255
resource representing a document's title	The histone methyltransferase DOT1L prevents antigen-independent differentiation and safeguards epigenetic identity of CD8+ T cells
schema:publication	bioRxiv
resource representing a document's body	covid:2f7564df663ecd0edf5d10113d70829e529d3116#body_text
is schema:about of	named entity 'histone methyltransferase' named entity 'effector' named entity 'loss' named entity 'Cytotoxic T-cell' named entity 'antigen' named entity 'REPRESSION' named entity 'EPIGENETIC MECHANISMS' named entity 'T-CELL' named entity 'CYTOTOXIC T-CELL' named entity 'REGULATED' covid:arg/2f7564df663ecd0edf5d10113d70829e529d3116 named entity 'T-cell' named entity 'fail' named entity 'signaling' named entity 'T-cell' named entity 'differentiation' named entity 'effector' named entity 'CD8' named entity 'defined' named entity 'nucleosome' named entity 'T cells' named entity 'barrier' named entity 'CD8 +' named entity 'T-cell' named entity 'ablation' named entity 'effector' named entity 'CD8 +' named entity 'nucleosome' named entity 'T-cell' named entity 'histone methyltransferase' named entity 'DOT1L' named entity 'Dot1L' named entity 'supporting' named entity 'CD8 +' named entity 'Dot1L' named entity 'Ezh2 gene' named entity 'methylated' named entity 'derepression' named entity 'IFNγ' named entity 'H3K79me2' named entity 'transgenic' named entity 'DOT1L' named entity 'TCR' named entity 'Dot1L' named entity 'spleen' named entity 'mice' named entity 'chromatin' named entity 'DOT1L' named entity 'Lck' named entity 'cell differentiation' named entity 'CD8 +' named entity 'transcriptome' named entity 'lymphocyte subsets' named entity 'staining' named entity 'CD44' named entity 'RNA-Seq' named entity 'Listeria monocytogenes' named entity 'p-value' named entity 'methylation' named entity 'CD44' named entity 'cell formation' named entity 'EDTA' named entity 'CD62L' named entity 'methylated' named entity 'differentially expressed genes' named entity 'Intracellular' named entity 'epigenome' named entity 'mouse model'

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