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| Status |
Public on Jul 28, 2020 |
| Title |
MYSM1 maintains ribosomal protein gene expression in hematopoietic stem cells to prevent hematopoietic dysfunction I. |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
MYSM1 is a transcriptional regulator essential for HSC function and hematopoiesis. We established that HSC dysfunction in Mysm1-deficiency is driven by p53 stress response, however, the molecular function of MYSM1 as a transcriptional activator and its essential role in p53 stress response repression remain difficult to reconcile. Here, we performed genome-wide analyses of MYSM1-regulated genes in hematopoietic stem and progenitor cells (HSPCs). This included RNA-Seq of sorted Mysm1-deficient mouse HSCs and MPPs, and ChIP-Seq mapping of MYSM1 DNA-binding sites in hematopoietic progenitor cell lines. We demonstrate a direct role for MYSM1 in the regulation of genes encoding protein components of the ribosome (RP-genes) and other regulators of translation. Mechanistically, the dysregulation of RP-genes in Mysm1-deficiency was upstream of p53-activation and associated with reduced HSCs protein synthesis rates and p53-dependent anemia.
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| Overall design |
To gain insight into the genomic regions directly regulated by MYSM1 in hematopoietic cells, we mapped MYSM1 DNA binding sites by ChIP-Seq. The experiments were carried out in two murine hematopoietic progenitor lines expressing triple-FLAG-tagged MYSM1: a multipotent progenitor line HPC7 widely used as a model to study transcriptional programs of hematopoiesis, and pro-B cell line Ba/F3 that was used in our previous work to model p53-activation and other molecular mechanisms of Mysm1-deficiency (Belle et al., 2016).
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| Contributor(s) |
Wang H, Belle J, Petrov J, Langlais D, Nijnik A |
| Citation(s) |
32641579, 34114734 |
| |
| Submission date |
May 15, 2020 |
| Last update date |
Jul 20, 2021 |
| Contact name |
David Langlais |
| E-mail(s) |
[email protected]
|
| Organization name |
McGill University
|
| Department |
Human Genetics
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| Lab |
Inflammation Genomics Lab
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| Street address |
740 Ave Dr Penfield, rm 4203, McGill Genome Centre
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| City |
MONTREAL |
| State/province |
QC |
| ZIP/Postal code |
H3A0G1 |
| Country |
Canada |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
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| Relations |
| BioProject |
PRJNA633123 |
| SRA |
SRP261865 |
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