Home > Publications Database > Aberrant chromatin landscape following loss of the H3.3 chaperone Daxx in haematopoietic precursors leads to Pu.1-mediated neutrophilia and inflammation. > print

001     163640
005     20231027131220.0
024 7 _ |a 10.1038/s41556-021-00774-y
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024 7 _ |a pmc:PMC8683376
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024 7 _ |a 1465-7392
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024 7 _ |a 1476-4679
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024 7 _ |a altmetric:118324437
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037 _ _ |a DZNE-2022-00386
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Gerber, Julia P
|0 P:(DE-2719)9002262
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|e First author
|u dzne
245 _ _ |a Aberrant chromatin landscape following loss of the H3.3 chaperone Daxx in haematopoietic precursors leads to Pu.1-mediated neutrophilia and inflammation.
260 _ _ |a New York, NY
|c 2021
|b Nature America
336 7 _ |a article
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520 _ _ |a 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.
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650 _ 7 |a Chromatin
|2 NLM Chemicals
650 _ 7 |a Co-Repressor Proteins
|2 NLM Chemicals
650 _ 7 |a Daxx protein, mouse
|2 NLM Chemicals
650 _ 7 |a Histones
|2 NLM Chemicals
650 _ 7 |a Molecular Chaperones
|2 NLM Chemicals
650 _ 7 |a Proto-Oncogene Proteins
|2 NLM Chemicals
650 _ 7 |a Retroelements
|2 NLM Chemicals
650 _ 7 |a Trans-Activators
|2 NLM Chemicals
650 _ 7 |a proto-oncogene protein Spi-1
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Autoimmune Diseases: genetics
|2 MeSH
650 _ 2 |a Autoimmune Diseases: pathology
|2 MeSH
650 _ 2 |a B-Lymphocytes: cytology
|2 MeSH
650 _ 2 |a Cell Line
|2 MeSH
650 _ 2 |a Chromatin: genetics
|2 MeSH
650 _ 2 |a Chromatin: pathology
|2 MeSH
650 _ 2 |a Co-Repressor Proteins: genetics
|2 MeSH
650 _ 2 |a Hematopoietic Stem Cells: cytology
|2 MeSH
650 _ 2 |a Histones: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Inflammation: pathology
|2 MeSH
650 _ 2 |a Leukocyte Disorders: congenital
|2 MeSH
650 _ 2 |a Leukocyte Disorders: pathology
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Mice, Knockout
|2 MeSH
650 _ 2 |a Molecular Chaperones: genetics
|2 MeSH
650 _ 2 |a Myelopoiesis: genetics
|2 MeSH
650 _ 2 |a Proto-Oncogene Proteins: metabolism
|2 MeSH
650 _ 2 |a Retroelements: genetics
|2 MeSH
650 _ 2 |a Skin Diseases: genetics
|2 MeSH
650 _ 2 |a Skin Diseases: immunology
|2 MeSH
650 _ 2 |a Skin Diseases: pathology
|2 MeSH
650 _ 2 |a Trans-Activators: metabolism
|2 MeSH
700 1 _ |a Russ, Jenny
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700 1 _ |a Chandrasekar, Vijay
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700 1 _ |a Offermann, Nina
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700 1 _ |a Lee, Hang-Mao
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700 1 _ |a Spear, Sarah
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700 1 _ |a Guzzi, Nicola
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700 1 _ |a Maida, Simona
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700 1 _ |a Pattabiraman, Sundararaghavan
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700 1 _ |a Zhang, Ruoyu
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700 1 _ |a Kayvanjoo, Amir H
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700 1 _ |a Datta, Preeta
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700 1 _ |a Kasturiarachchi, Jagath
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700 1 _ |a Sposito, Teresa
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700 1 _ |a Izotova, Natalia
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700 1 _ |a Händler, Kristian
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700 1 _ |a Adams, Peter D
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700 1 _ |a Marafioti, Teresa
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700 1 _ |a Enver, Tariq
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700 1 _ |a Wenzel, Jörg
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700 1 _ |a Beyer, Marc-Daniel
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700 1 _ |a Mass, Elvira
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700 1 _ |a Bellodi, Cristian
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700 1 _ |a Schultze, Joachim
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700 1 _ |a Capasso, Melania
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700 1 _ |a Nimmo, Rachael
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700 1 _ |a Salomoni, Paolo
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773 _ _ |a 10.1038/s41556-021-00774-y
|g Vol. 23, no. 12, p. 1224 - 1239
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