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BRIEF RESEARCH REPORT article

Front. Immunol.
Sec. T Cell Biology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1440044
This article is part of the Research Topic Gene Regulation in Lymphocyte Development and Response View all articles

TET proteins regulate Drosha expression and impact microRNAs in iNKT cells

Provisionally accepted
Marianthi Gioulbasani Marianthi Gioulbasani Tarmo Äijö Tarmo Äijö Jair E. Valenzuela Jair E. Valenzuela Julia Buquera Bettes Julia Buquera Bettes Ageliki Tsagaratou Ageliki Tsagaratou *
  • University of North Carolina at Chapel Hill, Chapel Hill, United States

The final, formatted version of the article will be published soon.

    DNA demethylases TET2 and TET3 play a fundamental role in thymic invariant natural killer T (iNKT) cell differentiation by mediating DNA demethylation of genes encoding for lineage specifying factors. Paradoxically, differential gene expression analysis revealed that significant number of genes were upregulated upon TET2 and TET3 loss in iNKT cells. This unexpected finding could be potentially explained if loss of TET proteins was reducing the expression of proteins that suppress gene expression. In this study, we discover that TET2 and TET3 synergistically regulate Drosha expression, by generating 5hmC across the gene body and by impacting chromatin accessibility. As DROSHA is involved in microRNA biogenesis, we proceed to investigate the impact of TET2/3 loss on microRNAs in iNKT cells.We report that among the downregulated microRNAs are members of the Let-7 family that downregulate in vivo the expression of the iNKT cell lineage specifying factor PLZF. Our data link TET proteins with microRNA expression and reveal an additional layer of TET mediated regulation of gene expression.

    Keywords: TET proteins, 5hmC, iNKT, Drosha, MicroRNAs, 12 pt Formatted: Font: 12 pt Formatted: Font: (Default) Arial, 12 pt, Font color: Auto

    Received: 28 May 2024; Accepted: 27 Aug 2024.

    Copyright: © 2024 Gioulbasani, Äijö, Valenzuela, Buquera Bettes and Tsagaratou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ageliki Tsagaratou, University of North Carolina at Chapel Hill, Chapel Hill, United States

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