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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 [CUT&Tag] |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Defective silencing of retroviral elements has been linked to inflamm-aging, cancer and auto-immune diseases. However, the underlying mechanisms are only partially understood. Here, we implicate the histone H3.3 chaperone Daxx, a retrotransposable element (RTE) repressor inactivated in myeloid leukemia and other neoplasms, in protection from inflammatory disease. Loss of Daxx has profound effects on chromatin landscapes and histone marks of hematopoietic progenitors, leading to engagement of a Pu.1-dependent transcriptional program for myelopoiesis at the expense of B-cell differentiation. This causes neutrophilia and inflammation, predisposing mice to development of an autoinflammatory skin disease. These molecular and phenotypic perturbations are in part reverted in animals lacking both Pu.1 and Daxx. However, hematopoietic progenitors in these mice also show unique chromatin and transcriptome alterations, suggesting synergistic interaction between the two pathways. Overall, our findings implicate RTE silencing in hematopoiesis and reveal a potential functional relationship between the H3.3 loading machinery and the pioneer transcription factor Pu.1.
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Overall design |
Examination of gene expression profiles, chromatin accessibility and epigenetic changes in hematopoietic stem/progenitor cells comparing wild-type and Daxx knock-out cells.
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Contributor(s) |
Gerber JP, Russ J, Chandrasekar V, Offermann N, Lee H, Spear S, Guzzi N, Maida S, Pattabiraman S, Zhang R, Kayvanjoo AH, Datta P, Kasturiarachchi J, Sposito T, Izotova N, Händler K, Adams PD, Marafioti T, Enver T, Wenzel J, Beyer M, Mass E, Bellodi C, Schultze JL, Capasso M, Nimmo R, Salomoni P |
Citation(s) |
34876685 |
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Submission date |
Mar 05, 2021 |
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) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (62)
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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 |
PRJNA707037 |
SRA |
SRP309493 |
Supplementary file |
Size |
Download |
File type/resource |
GSE168367_DaxxFFPu1FF_24wpi_H3.3_cov.bw |
392.4 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxFFPu1FF_24wpi_H3K27ac_cov.bw |
252.2 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxFFPu1FF_24wpi_H3K27me3_cov.bw |
415.7 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxFFPu1FF_24wpi_H3K9me3_cov.bw |
172.9 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxFFPu1FF_8wpi_H3K27me3_cov.bw |
143.4 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxFFPu1FF_8wpi_H3K9me3_cov.bw |
119.6 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxFF_24wpi_H3K27ac_cov.bw |
273.5 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxFF_24wpi_H3K27me3_cov.bw |
495.8 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxFF_24wpi_H3K9me3_cov.bw |
325.2 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxFF_24wpi_Pu1_cov.bw |
160.2 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxFF_3wpi_H3.3_cov.bw |
338.7 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxFF_3wpi_H3K27ac_cov.bw |
84.6 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxFF_3wpi_H3K9me3_cov.bw |
95.1 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxFF_3wpi_Pu1_cov.bw |
423.5 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxFF_8wpi_H3K27me3_cov.bw |
140.8 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxFF_8wpi_H3K9me3_cov.bw |
104.7 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxWtWt_24wpi_H3.3_cov.bw |
179.7 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxWtWt_24wpi_H3K27ac_cov.bw |
331.5 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxWtWt_24wpi_H3K27me3_cov.bw |
436.6 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxWtWt_24wpi_H3K9me3_cov.bw |
264.3 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxWtWt_24wpi_Pu1_cov.bw |
178.6 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxWtWt_3wpi_H3.3_cov.bw |
437.4 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxWtWt_3wpi_H3K27ac_cov.bw |
107.1 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxWtWt_3wpi_H3K9me3_cov.bw |
132.7 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxWtWt_3wpi_Pu1_cov.bw |
533.5 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxWtWt_8wpi_H3K27me3_cov.bw |
138.5 Mb |
(ftp)(http) |
BW |
GSE168367_DaxxWtWt_8wpi_H3K9me3_cov.bw |
116.3 Mb |
(ftp)(http) |
BW |
GSE168367_H3.3_DaxxFF_24wpi_noXY_diffsite.txt.gz |
16.9 Mb |
(ftp)(http) |
TXT |
GSE168367_H3.3_DaxxFF_3wpi_diffsite.txt.gz |
9.8 Mb |
(ftp)(http) |
TXT |
GSE168367_H3K27ac_DaxxFF_24wpi_noXY_diffsite.txt.gz |
13.4 Mb |
(ftp)(http) |
TXT |
GSE168367_H3K27ac_DaxxFF_diffsite.txt.gz |
6.0 Mb |
(ftp)(http) |
TXT |
GSE168367_H3K27me3_DaxxFFPu1FFvsDaxxFF_8wpi_diffsite.txt.gz |
4.2 Mb |
(ftp)(http) |
TXT |
GSE168367_H3K27me3_DaxxFFPu1FFvsDaxxWtWt_8wpi_diffsite.txt.gz |
4.4 Mb |
(ftp)(http) |
TXT |
GSE168367_H3K27me3_DaxxFF_24wpi_noXY_diffsite.txt.gz |
9.3 Mb |
(ftp)(http) |
TXT |
GSE168367_H3K27me3_DaxxFFvsDaxxWtWt_8wpi_diffsite.txt.gz |
16.7 Mb |
(ftp)(http) |
TXT |
GSE168367_H3K9me3_DaxxFFPu1FFvsDaxxFF_8wpi_diffsite.txt.gz |
2.9 Mb |
(ftp)(http) |
TXT |
GSE168367_H3K9me3_DaxxFFPu1FFvsDaxxWtWt_8wpi_diffsite.txt.gz |
3.3 Mb |
(ftp)(http) |
TXT |
GSE168367_H3K9me3_DaxxFF_24wpi_noXY_diffsite.txt.gz |
10.2 Mb |
(ftp)(http) |
TXT |
GSE168367_H3K9me3_DaxxFF_8wpi_diffsite.txt.gz |
4.8 Mb |
(ftp)(http) |
TXT |
GSE168367_H3K9me3_DaxxFF_diffsite.txt.gz |
3.6 Mb |
(ftp)(http) |
TXT |
GSE168367_Pu1_DaxxFF_24wpi_noXY_diffsite.txt.gz |
17.0 Mb |
(ftp)(http) |
TXT |
GSE168367_Pu1_DaxxFF_3wpi_diffsite.txt.gz |
10.9 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |