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The histone lysine methyltransferase MLL1 regulates the activation and functional specialization of regulatory T cells [ChIP-seq]

GSE248781 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 8 samples Submitted 2025/05/02 Platform GPL17021
Summary
The activation and specialization of regulatory T cells (Tregs) are crucial for maintaining immune self-tolerance, but the epigenetic regulation of these processes remains largely unexplored. Here, we show that T-cell-specific deletion of the lysine methyltransferase MLL1 results in a spontaneous lymphocyte proliferation phenotype in aged mice without disturbing the development of conventional T cells and Tregs. Treg-specific MLL1 ablation leads to a systemic autoimmune disease associated with Treg dysfunction. RNA sequencing demonstrated that the induction of multiple genes involved in Treg activation, functional specialization and tissue immigration is defective in MLL1-deficient Tregs. This dysregulation is associated with defects in H3K4 trimethylation at the transcription start sites (TSSs) of these genes. Finally, using a T-bet fate-mapping mouse system, we determined that MLL1 is required to establish stable Th1-type Tregs. Thus, MLL1 plays an essential role in optimal Treg function by providing a coordinated epigenetic context for activation and specialization.
Published in
The histone lysine methyltransferase MLL1 regulates the activation and functional specialization of regulatory T cells
Wang T, Guo J, Liping Li et al. · Cell reports 2024 · PMID 38735046 · doi:10.1016/j.celrep.2024.114222
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Also filed as BioProject PRJNA1046006 and SRA study SRP474812. Searching any of these in the dataset finder brings you back here.

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