Research Papers - School of Education

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Author: search.filters.author.Kasturiarachchi, J. CSubject: search.filters.subject.H3.3 chaperone Daxx

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    PublicationOpen Access
    Author Correction: Aberrant chromatin landscape following loss of the H3. 3 chaperone Daxx in haematopoietic precursors leads to Pu. 1-mediated neutrophilia and inflammation
    (Nature Publishing Group, 2022-01-04) Gerber, J. P; Russ, J; Chandrasekar, V; Offermann, N; Lee, H. M; Spear, S; Guzzi, N; Maida, S; Pattabiraman, S; Zhang, R; Kayvanjoo, A. H; Datta, P; Kasturiarachchi, J. C; Sposito, T; Izotova, N; Händler, K; Adams, P. D; Marafioti, T; Enver, T; Wenzel, J; Beyer, M; Mass, E; Bellodi, C; Schultze, J. L; Capasso, M; Nimmo, R; Salomoni, P
    In the version of this article initially published, there were omissions in the Acknowledgements section. The section has been amended to now include thanks to Daniele Bano, Miriam Stork and other members of their team (DZNE). We also thank Steven Zvi Josefowicz (Cornell University), Hugues de The (College De France/INSERM) and Nada Jabado (McGill University) for input and discussion, Bart Vanhaesebroeck (UCL) for providing the Rosa26CreERT2 mice, the P.S. lab (in particular, Xin Yan, Christina Georgopoulou Manon Chevallot-Beroux and D.A.) for assistance with experiments and scientific discussion, the DZNE Core Facilities, DZNE animal facility, PRECISE, the LIMES animal facility, UCL Core Services and UCL Biological Services.
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    PublicationOpen Access
    Aberrant chromatin landscape following loss of the H3. 3 chaperone Daxx in haematopoietic precursors leads to Pu. 1-mediated neutrophilia and inflammation
    (Nature Publishing Group, 2021-12) Gerber, J. P; Russ, J; Chandrasekar, V; Offermann, N; Lee, H. M; Spear, S; Guzzi, N; Maida, S; Pattabiraman, S; Zhang, R; Kayvanjoo, A. H; Datta, P; Kasturiarachchi, J. C; Sposito, T; Izotova, N; Händler, K; Adams, P. T; Marafioti, T; Enver, T; Wenzel, J; Beyer, M; Mass, E; Bellodi, C; Schultze, J. L; Capasso, M; Nimmo, R; Salomoni, P
    Defective silencing of retrotransposable elements has been linked to inflammageing, cancer and autoimmune diseases. However, the underlying mechanisms are only partially understood. Here we implicate the histone H3.3 chaperone Daxx, a retrotransposable element repressor inactivated in myeloid leukaemia and other neoplasms, in protection from inflammatory disease. Loss of Daxx alters the chromatin landscape, H3.3 distribution and histone marks of haematopoietic progenitors, leading to engagement of a Pu.1-dependent transcriptional programme for myelopoiesis at the expense of B-cell differentiation. This causes neutrophilia and inflammation, predisposing mice to develop an autoinflammatory skin disease. While these molecular and phenotypic perturbations are in part reverted in animals lacking both Pu.1 and Daxx, haematopoietic progenitors in these mice show unique chromatin and transcriptome alterations, suggesting an interaction between these two pathways. Overall, our findings implicate retrotransposable element silencing in haematopoiesis and suggest a cross-talk between the H3.3 loading machinery and the pioneer transcription factor Pu.1.