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| Status |
Public on Mar 13, 2020 |
| Title |
Genome-wide maps of chromatin state in HSC, HPC7 and lineage-committed cells |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The correct balance between self-renewal and differentiation of hematopoietic stem cells (HSC) is orchestrated by the crosstalk between extrinsic and intrinsic factors. A combination of transcriptional regulators and chromatin-based epigenetic changes provide a fine-tuning mechanism to determine HSC fate. We report that the histone H4 lysine 16 (H4K16) specific lysine acetyl-transferase MOF (KAT8) shows dynamic chromatin occupancy during HSC differentiation. MOF regulates erythroid commitment by regulating the expression of key haematopoietic genes. Indeed, loss of just one copy of Mof perturbs HSC commitment, leading to skewed granulocytic lineage commitment and impaired erythroid maturation in mice. Wild-type MOF and strikingly, enforced expression of the transcription factor GATA-1, rescued hematopoietic skewing of this granulocytic fate bias. Furthermore, single-cell RNA-seq of Mof haploinsufficient HSCs revealed an enrichment of a novel immature heterogeneous sub-population of cells with increased proliferation potential, indicative of an enhanced pro-leukemic state. Therefore, our results demonstrate an unprecedented role of MOF in the regulation of HSC plasticity, identity and differentiation.
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| Overall design |
We performed MOF ChIP-seq in primary HSCs and MEPs from wild type and Mof-heterozygous animals. And H4K16ac profile in the haematopoeitic progenitor cell line (HPC7). Antibodies used for ChiP anti-MOF (#A300-992A, Bethyl), GATA-1 (#181544, Abcam), H4K16ac (#07-329, Millipore)
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| Web link |
https://doi.org/10.1126/sciadv.aaz4815
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| |
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| Contributor(s) |
Rodrigues CP, Akhtar A |
| Citation(s) |
32671208 |
| |
| Submission date |
Nov 20, 2017 |
| Last update date |
Jul 20, 2020 |
| Contact name |
Asifa Akhtar |
| E-mail(s) |
akhtarlab_data@ie-freiburg.mpg.de
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| Organization name |
Max Planck Institute of Immunobiology and Epigenetics
|
| Department |
Chromatin Regulation
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| Lab |
Akhtar Lab
|
| Street address |
Stuebeweg 51
|
| City |
Freiburg |
| ZIP/Postal code |
79108 |
| Country |
Germany |
| |
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| Platforms (1) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE107154 |
Decoding the regulatory circuit by epigenetic regulator MOF in haematopoiesis |
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| Relations |
| BioProject |
PRJNA419184 |
| SRA |
SRP125306 |
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