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Title: Aberrant chromatin landscape following loss of the H3. 3 chaperone Daxx in haematopoietic precursors leads to Pu. 1-mediated neutrophilia and inflammation
Authors: 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
Keywords: Aberrant chromatin landscape
H3.3 chaperone Daxx
haematopoietic precursors leads
Pu.1-mediated neutrophilia
Issue Date: Dec-2021
Publisher: Nature Publishing Group
Series/Report no.: Nature cell biology;Vol 23 Issue 12 Pages 1224-1239
Abstract: 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.
URI: http://localhost:80/handle/123456789/723
ISSN: 1465-7392
Appears in Collections:Research Papers
Research Papers - School of Education
Research Papers - SLIIT Staff Publications

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