Dataset Information

MS-based characterization of YTHDC1 interactome

ABSTRACT: Heat shock induces a cell response leading to profound changes in genome expression. Recently, N6-methyladenosine (m6A) RNA modification has been implicated in this response, but with limited information of its role in the heat-induced reprograming of gene expression. Most of m6A molecular and cellular functions rely on m6A readers and the best characterized m6A readers are members of the YTH-domain-containing protein family present from yeast to humans. To investigate the function of the nuclear m6A reader YTHDC1, we characterized its binding partners.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Fibroblast

SUBMITTER: Yohann Couté

LAB HEAD: Yohann Couté

PROVIDER: PXD037414 | Pride | 2023-01-11

REPOSITORIES: Pride

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Publications

Chromatin-associated YTHDC1 coordinates heat-induced reprogramming of gene expression.

Timcheva Kalina K Dufour Solenne S Touat-Todeschini Leila L Burnard Callum C Carpentier Marie-Christine MC Chuffart Florent F Merret Rémy R Helsmoortel Marion M Ferré Sabrina S Grézy Aude A Couté Yohann Y Rousseaux Sophie S Khochbin Saadi S Vourc'h Claire C Bousquet-Antonelli Cécile C Kiernan Rosemary R Seigneurin-Berny Daphné D Verdel André A

Cell reports 20221201 11

Heat stress (HS) induces a cellular response leading to profound changes in gene expression. Here, we show that human YTHDC1, a reader of N6-methyladenosine (m6A) RNA modification, mostly associates to the chromatin fraction and that HS induces a redistribution of YTHDC1 across the genome, including to heat-induced heat shock protein (HSP) genes. YTHDC1 binding to m6A-modified HSP transcripts co-transcriptionally promotes expression of HSPs. In parallel, hundreds ...[more]

PMID: 36516773

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Project description:Introduction: Expansion of antigen (Ag)-specific natural occurring regulatory T cells (nTregs) is required to obtain sufficient numbers of cells for cellular immunotherapy. In this study, different allogeneic stimuli were studied for their capacity to generate functional alloAg-specific nTregs. Methods: A highly enriched nTreg-fraction (CD4+CD25brightCD127- T cells) was alloAg-specific expanded using HLA-mismatched immature, mature monocyte-derived dendritic cells (moDC) or peripheral blood mononuclear cells (PBMC). The allogeneic mature moDC-expanded nTregs were fully characterized by analysis of the demethylation status within the TSDR of the FOXP3 gene and the expression of both protein and mRNA of FOXP3, HELIOS, CTLA4 and cytokines. In addition, the antigen-specific suppressive capacity of these expanded nTregs was tested. Results: Allogeneic mature moDC and skin-derived DC were superior in inducing nTreg-expansion compared to immature moDC or PBMC in an HLA-DR and CD80/CD86-dependent way. Remarkably, the presence of exogenous IL-15 without IL-2, could facilitate optimal mature moDC-induced nTreg-expansion. Allogeneic mature moDC-expanded nTregs were at low ratios (<1:320), potent suppressors of alloAg-induced proliferation without significant suppression of completely HLA-mismatched-Ag-induced proliferation. Mature moDC-expanded nTregs were highly demethylated at the TSDR within the FOXP3 gene and highly expressed of FOXP3, HELIOS and CTLA4. A minority of the expanded nTregs produced IL-10, IL-2, IFN-g and TNF-a but very few IL-17 producing nTregs were found. Next generation sequencing of mRNA of moDC-expanded nTregs revealed a strong induction of Treg-associated mRNAs. Conclusions: Human allogeneic mature moDC are highly efficient stimulator cells, in presence of exogenous IL-15, for expansion of stable alloAg-specific nTregs with superior suppressive function. Four different batches of highly pure regulatory T cells (all from the same donor) were expanded in two different ways, and compared to non-expanded samples.

Dataset Information

MS-based characterization of YTHDC1 interactome

Publications

Chromatin-associated YTHDC1 coordinates heat-induced reprogramming of gene expression.

Similar Datasets

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