|
| Status |
Public on Sep 26, 2019 |
| Title |
Cohesin Members Stag1 and Stag2 Display Distinct Roles in Chromatin Accessibility and Topological Control of HSC Self-Renewal and Differentiation [ATAC_LSK_GMP_CFUE_Stag2KOWT] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Transcriptional regulators, including the cohesin complex member STAG2, are recurrently mutated in cancer. The role of STAG2 in gene regulation, hematopoiesis, and tumor suppression remains unresolved. We show that Stag2 deletion in hematopoietic stem and progenitor cells (HSPCs) results in altered hematopoietic function, increased self-renewal, and impaired differentiation. Chromatin immunoprecipitation (ChIP) sequencing revealed that, although Stag2 and Stag1 bind a shared set of genomic loci, a component of Stag2 binding sites is unoccupied by Stag1, even in Stag2-deficient HSPCs. Although concurrent loss of Stag2 and Stag1 abrogated hematopoiesis, Stag2 loss alone decreased chromatin accessibility and transcription of lineage-specification genes, including Ebf1 and Pax5, leading to increased self-renewal and reduced HSPC commitment to the B cell lineage. Our data illustrate a role for Stag2 in transformation and transcriptional dysregulation distinct from its shared role with Stag1 in chromosomal segregation.
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| |
|
| Overall design |
ATAC-seq of Stag2 KO and WT LSK, GMP, and CFU-E cells
|
| |
|
| Contributor(s) |
Viny AD, Koche RP, Levine RL |
| Citation(s) |
31495782 |
| |
| Submission date |
Sep 25, 2019 |
| Last update date |
Sep 28, 2019 |
| Contact name |
Richard Koche |
| E-mail(s) |
[email protected]
|
| Organization name |
Memorial Sloan Kettering Cancer Center
|
| Street address |
417 E. 68th St.
|
| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (14)
|
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| This SubSeries is part of SuperSeries: |
| GSE135031 |
Stag1 and Stag2 regulate cell fate decisions in hematopoiesis through non-redundant topological control |
|
| Relations |
| BioProject |
PRJNA574134 |
| SRA |
SRP223256 |
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