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@ARTICLE{Gerber:163640,
author = {Gerber, Julia P and Russ, Jenny and Chandrasekar, Vijay and
Offermann, Nina and Lee, Hang-Mao and Spear, Sarah and
Guzzi, Nicola and Maida, Simona and Pattabiraman,
Sundararaghavan and Zhang, Ruoyu and Kayvanjoo, Amir H and
Datta, Preeta and Kasturiarachchi, Jagath and Sposito,
Teresa and Izotova, Natalia and Händler, Kristian and
Adams, Peter D and Marafioti, Teresa and Enver, Tariq and
Wenzel, Jörg and Beyer, Marc-Daniel and Mass, Elvira and
Bellodi, Cristian and Schultze, Joachim and Capasso, Melania
and Nimmo, Rachael and Salomoni, Paolo},
title = {{A}berrant chromatin landscape following loss of the {H}3.3
chaperone {D}axx in haematopoietic precursors leads to
{P}u.1-mediated neutrophilia and inflammation.},
journal = {Nature cell biology},
volume = {23},
number = {12},
issn = {1465-7392},
address = {New York, NY},
publisher = {Nature America},
reportid = {DZNE-2022-00386},
pages = {1224 - 1239},
year = {2021},
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.},
keywords = {Animals / Autoimmune Diseases: genetics / Autoimmune
Diseases: pathology / B-Lymphocytes: cytology / Cell Line /
Chromatin: genetics / Chromatin: pathology / Co-Repressor
Proteins: genetics / Hematopoietic Stem Cells: cytology /
Histones: metabolism / Humans / Inflammation: pathology /
Leukocyte Disorders: congenital / Leukocyte Disorders:
pathology / Mice / Mice, Inbred C57BL / Mice, Knockout /
Molecular Chaperones: genetics / Myelopoiesis: genetics /
Proto-Oncogene Proteins: metabolism / Retroelements:
genetics / Skin Diseases: genetics / Skin Diseases:
immunology / Skin Diseases: pathology / Trans-Activators:
metabolism / Chromatin (NLM Chemicals) / Co-Repressor
Proteins (NLM Chemicals) / Daxx protein, mouse (NLM
Chemicals) / Histones (NLM Chemicals) / Molecular Chaperones
(NLM Chemicals) / Proto-Oncogene Proteins (NLM Chemicals) /
Retroelements (NLM Chemicals) / Trans-Activators (NLM
Chemicals) / proto-oncogene protein Spi-1 (NLM Chemicals)},
cin = {AG Salomoni / Schultze - PRECISE / $R\&D$ PRECISE / AG
Capasso / AG Bano / AG Beyer},
ddc = {570},
cid = {I:(DE-2719)1013032 / I:(DE-2719)1013031 /
I:(DE-2719)5000031 / I:(DE-2719)1013033 / I:(DE-2719)1013003
/ I:(DE-2719)1013035},
pnm = {352 - Disease Mechanisms (POF4-352) / 351 - Brain Function
(POF4-351) / 354 - Disease Prevention and Healthy Aging
(POF4-354)},
pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-351 /
G:(DE-HGF)POF4-354},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34876685},
pmc = {pmc:PMC8683376},
doi = {10.1038/s41556-021-00774-y},
url = {https://pub.dzne.de/record/163640},
}