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| Status |
Public on Aug 31, 2021 |
| Title |
Aberrant chromatin landscape upon loss of the H3.3 chaperone Daxx leads to Pu.1-mediated neutrophilia and inflammation [ATAC-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The lymphoid and myeloid lineages are in equilibrium during steady-state hematopoiesis. Tilting hematopoiesis towards innate immunity has been linked to inflammation and may predispose to myeloproliferative disease. Although epigenetic players have been implicated in the control of hematopoiesis and pathogenesis of blood neoplasms, the role of chromatin-based mechanisms in regulating the lymphoid/myeloid balance remains only partially understood. Here, we show that loss of the H3.3 chaperone Daxx causes myeloid skewing, neutrophilia and pyoderma gangrenosum-like lesions, a human skin disease of unknown etiology. Daxx deficiency leads to chromatin opening at intergenic regions, including TERRA target sites, deregulation of repeat elements and activation of anti-viral defense pathways. Finally, the other main H3.3 chaperone, Hira, is dispensable for normal hematopoiesis but supports expansion of Daxx-deficient neutrophils. These results define a role for Daxx in proper selection of lymphoid versus myeloid lineages, linked to control of repeat elements and anti-inflammatory responses.
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| Overall design |
Examination of gene expression profiles and chromatin accessibility in hematopoietic stem/progenitor cells comparing wild-type and Daxx knock-out cells.
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| Contributor(s) |
Hofmann J, Russ J, Spear S, Guzzi N, Chandrasekar V, Izotova N, Maida S, Händler K, Adams P, Marafioti T, Enver T, Wenzel J, Beyer M, Bellodi C, Schultze J, Capasso M, Nimmo R, Salomoni P |
| Citation(s) |
34876685 |
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| Submission date |
Aug 31, 2018 |
| Last update date |
Jan 11, 2022 |
| Contact name |
Paolo Salomoni |
| E-mail(s) |
paolo.salomoni@dzne.de
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| Organization name |
DZNE e.V.
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| Street address |
Sigmund-Freud-Str. 27
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| City |
Bonn |
| ZIP/Postal code |
53127 |
| Country |
Germany |
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| Platforms (2) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (24)
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| This SubSeries is part of SuperSeries: |
| GSE119309 |
Aberrant chromatin landscape upon loss of the H3.3 chaperone Daxx leads to Pu.1-mediated neutrophilia and inflammation |
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| Relations |
| BioProject |
PRJNA488721 |
| SRA |
SRP159236 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE119306_180606_CMPff_EncodePeaks_m.bed.gz |
414.0 Kb |
(ftp)(http) |
BED |
| GSE119306_180606_CMPwt_EncodePeaks_m.bed.gz |
536.9 Kb |
(ftp)(http) |
BED |
| GSE119306_180606_GMPff_EncodePeaks_m.bed.gz |
404.8 Kb |
(ftp)(http) |
BED |
| GSE119306_180606_GMPwt_EncodePeaks_m.bed.gz |
528.7 Kb |
(ftp)(http) |
BED |
| GSE119306_180606_LTHSCff_EncodePeaks_m.bed.gz |
578.5 Kb |
(ftp)(http) |
BED |
| GSE119306_180606_LTHSCwt_EncodePeaks_m.bed.gz |
538.0 Kb |
(ftp)(http) |
BED |
| GSE119306_DaxxFF.idr.conservative_peak.narrowPeak.gz |
2.0 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE119306_DaxxWtWt.idr.conservative_peak.narrowPeak.gz |
1.6 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE119306_KLS_ATACseq_DaxxFFPu1FFvsDaxxWtWt_diffsite.txt.gz |
3.4 Mb |
(ftp)(http) |
TXT |
| GSE119306_KLS_ATACseq_DaxxFF_diffsite.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE119306_KLS_DKO.idr.conservative_peak.narrowPeak.gz |
921.2 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE119306_KLS_DaxxFF.idr.conservative_peak.narrowPeak.gz |
1.8 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE119306_KLS_Wildtype.idr.conservative_peak.narrowPeak.gz |
1.3 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE119306_LTHSC_ATACseq_3dpi_DaxxFFvsDaxxWtWt_diffsite.txt.gz |
824.5 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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