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  • Gerber, Julia P.German Center for Neurodegenerative Diseases (DZNE), Bonn,UCL Cancer Institute (author)

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

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-12-07
  • Springer Science and Business Media LLC,2021
  • 16 s.

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:2b8f138f-de5e-4f02-8aa9-c94d0f7dc7cd
  • https://lup.lub.lu.se/record/2b8f138f-de5e-4f02-8aa9-c94d0f7dc7cdURI
  • https://doi.org/10.1038/s41556-021-00774-yDOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Russ, JennyGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Chandrasekar, VijayGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Offermann, NinaGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Lee, Hang MaoGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Spear, SarahQueen Mary University (author)
  • Guzzi, NicolaLund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-ngz (author)
  • Maida, SimonaGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Pattabiraman, SundararaghavanGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Zhang, RuoyuGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Kayvanjoo, Amir H.University of Bonn (author)
  • Datta, PreetaUCL Cancer Institute (author)
  • Kasturiarachchi, JagathUCL Cancer Institute (author)
  • Sposito, TeresaGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Izotova, NataliaUCL Cancer Institute (author)
  • Händler, KristianGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Adams, Peter D.Sanford Burnham Prebys Medical Discovery Institute (author)
  • Marafioti, TeresaUniversity College London,UCL Cancer Institute (author)
  • Enver, TariqUCL Cancer Institute(Swepub:lu)med-tqe (author)
  • Wenzel, JörgUniversity Hospital Bonn (author)
  • Beyer, MarcGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Mass, ElviraUniversity of Bonn (author)
  • Bellodi, CristianLund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,RNA och stamcellsbiologi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine,RNA and Stem Cell Biology,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)med-cnb (author)
  • Schultze, Joachim L.University of Bonn,German Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Capasso, MelaniaQueen Mary University,German Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Nimmo, RachaelUCL Cancer Institute (author)
  • Salomoni, PaoloUCL Cancer Institute,German Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • German Center for Neurodegenerative Diseases (DZNE), BonnUCL Cancer Institute (creator_code:org_t)

Related titles

  • In:Nature Cell Biology: Springer Science and Business Media LLC23:12, s. 1224-12391465-73921476-4679

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