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Drosophila TET acts with PRC1 to activate gene expression independently of its catalytic activity

Gilbert, Guerric, Renaud, Yoan, Teste, Camille, Anglaret, Nadège, Bertrand, Romane, Hoehn, Sven, Jurkowski, Tomasz P. ORCID: https://orcid.org/0000-0002-2012-0240, Schuettengruber, Bernd, Cavalli, Giacomo, Waltzer, Lucas and Vandel, Laurence 2024. Drosophila TET acts with PRC1 to activate gene expression independently of its catalytic activity. Science Advances 10 (18) , eadn5861. 10.1126/sciadv.adn5861

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Abstract

Enzymes of the ten-eleven translocation (TET) family play a key role in the regulation of gene expression by oxidizing 5-methylcytosine (5mC), a prominent epigenetic mark in many species. Yet, TET proteins also have less characterized noncanonical modes of action, notably in Drosophila, whose genome is devoid of 5mC. Here, we show that Drosophila TET activates the expression of genes required for larval central nervous system (CNS) development mainly in a catalytic-independent manner. Genome-wide profiling shows that TET is recruited to enhancer and promoter regions bound by Polycomb group complex (PcG) proteins. We found that TET interacts and colocalizes on chromatin preferentially with Polycomb repressor complex 1 (PRC1) rather than PRC2. Furthermore, PRC1 but not PRC2 is required for the activation of TET target genes. Last, our results suggest that TET and PRC1 binding to activated genes is interdependent. These data highlight the importance of TET noncatalytic function and the role of PRC1 for gene activation in the Drosophila larval CNS.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: American Association for the Advancement of Science
ISSN: 2375-2548
Date of First Compliant Deposit: 13 May 2024
Date of Acceptance: 3 April 2024
Last Modified: 16 May 2024 09:15
URI: https://orca.cardiff.ac.uk/id/eprint/168865

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