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The Drosophila MOZ homolog Enok controls Notch-dependent induction of the RUNX gene lozenge independently of its histone-acetyl transferase activity

Thomas Genais, Delhia Gigan, Benoit Augé, Douaa Moussalem, View ORCID ProfileLucas Waltzer, View ORCID ProfileMarc Haenlin, View ORCID ProfileVanessa Gobert
doi: https://doi.org/10.1101/2020.07.27.222620
Thomas Genais
1CBD, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse 31062, France
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Delhia Gigan
1CBD, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse 31062, France
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Benoit Augé
1CBD, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse 31062, France
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Douaa Moussalem
1CBD, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse 31062, France
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Lucas Waltzer
1CBD, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse 31062, France
2University of Clermont Auvergne, CNRS, Inserm, GReD, Clermont-Ferrand, France
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Marc Haenlin
1CBD, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse 31062, France
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  • For correspondence: vanessa.gobert@univ-tlse3.fr marc.haenlin@univ-tlse3.fr
Vanessa Gobert
1CBD, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse 31062, France
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  • ORCID record for Vanessa Gobert
  • For correspondence: vanessa.gobert@univ-tlse3.fr marc.haenlin@univ-tlse3.fr
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Abstract

The human KAT6 lysine acetyltransferase MOZ has been shown to be an essential player in the field of normal and malignant hematopoiesis. It belongs to a highly conserved family of epigenetic factors and remodels chromatin by acetylating histone tails in association with its partners of the ING5 complex. Here, we report that its Drosophila counterpart Enok is required during larval hematopoiesis to control the Notch-dependent induction of circulating crystal cells. In particular enok is essential to allow expression of the RUNX factor Lozenge (Lz) that controls the crystal cell specific transcriptional program. We demonstrate that this function involves neither the Eaf6 and Ing5 subunits of the Drosophila ING5 complex, nor Enok own acetyltransferase activity. We identify in lz third intron a hematopoietic enhancer, which is both required to promote expression in Notch-activated crystal cell precursors in an enok-dependent manner and bound by Enok. The non-catalytic mode of action of Enok is likely conserved in MOZ/KAT6 proteins and might be of high relevance in mammalian hematopoiesis, whether normal or malignant.

Competing Interest Statement

The authors have declared no competing interest.

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Posted July 28, 2020.
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The Drosophila MOZ homolog Enok controls Notch-dependent induction of the RUNX gene lozenge independently of its histone-acetyl transferase activity
Thomas Genais, Delhia Gigan, Benoit Augé, Douaa Moussalem, Lucas Waltzer, Marc Haenlin, Vanessa Gobert
bioRxiv 2020.07.27.222620; doi: https://doi.org/10.1101/2020.07.27.222620
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The Drosophila MOZ homolog Enok controls Notch-dependent induction of the RUNX gene lozenge independently of its histone-acetyl transferase activity
Thomas Genais, Delhia Gigan, Benoit Augé, Douaa Moussalem, Lucas Waltzer, Marc Haenlin, Vanessa Gobert
bioRxiv 2020.07.27.222620; doi: https://doi.org/10.1101/2020.07.27.222620

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