|
| Status |
Public on Mar 25, 2021 |
| Title |
DNA accessibility determines the level of Notch signal strength necessary for lineage specific target gene expression (Dnase-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Using the Notch signaling pathway, hematopoietic stem and progenitor cells (HSPC) sense and respond to the surrounding microenvironment to regulate cell fate outcome. Our previous studies have indicated that quantitative differences in Notch signal strength mediate cell-fate decisions during hematopoiesis. Low signal strength favors HSPC self-renewal, along with inhibition of myelopoiesis, whereas high signal strength promotes T cell differentiation. The basis for target gene selectivity in response to quantitative differences in Notch signal strength is unknown. Focusing on the high dose dependent induction of the T cell lineage, we found that targets essential for T cell commitment, including IL2ra, CD3 and Rag1, establish promoter DNA accessibility only upon exposure to high levels of Notch signaling. We further find that low promoter CpG content is a feature capable of maintaining the ground state DNA inaccessibility of these lineage determining genes. Our results suggest that DNA inaccessibility at the promoters of essential T cell commitment genes, mediated in part through low CpG content, provides robust protection against stochastic activation in inappropriate Notch signaling contexts, ensuring the maintenance of HSPC developmental plasticity.
|
| |
|
| Overall design |
DNase-seq data was collected across different stages of T cell development (LSK, DN1, DN2a, DN2b) and negative control (IgG), where each stage has 2 to 3 replicates. To find the accessible regions genome-wide, a peak calling approach hotspot2 was applied on each stage respectively, and in total ~170,000 DHSs regions was identified with peaks.
|
| |
|
| Contributor(s) |
Furuyama S, Sandstrom R |
| Citation(s) |
33770495 |
| |
| Submission date |
Dec 30, 2019 |
| Last update date |
May 06, 2021 |
| Contact name |
John A Stamatoyannopoulos |
| E-mail(s) |
jstam@altius.org
|
| Organization name |
Altius Institute / University of Washington
|
| Department |
Genome Sciences
|
| Lab |
Stamatoyannopoulos
|
| Street address |
2211 Elliott Avenue, 6th Floor
|
| City |
SEATTLE |
| State/province |
WA |
| ZIP/Postal code |
98121 |
| Country |
USA |
| |
|
| Platforms (3) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (12)
|
|
| This SubSeries is part of SuperSeries: |
| GSE142739 |
DNA accessibility determines the level of Notch signal strength necessary for lineage specific target gene expression |
|
| Relations |
| BioProject |
PRJNA598169 |
| SRA |
SRP239081 |
Less...
More...