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| Status |
Public on Apr 07, 2020 |
| Title |
Combined Cohesin-Runx1 Deficiency Synergistically Perturbs Chromatin Looping and Causes Myelodysplastic Syndromes [Hi-C] |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Other
|
| Summary |
STAG2 encodes a cohesin component and is frequently mutated in myeloid neoplasms, showing highly significant co-mutation patterns with other drivers, including RUNX1. However, the molecular basis of cohesin-mutated leukemogenesis remains poorly understood. Here we show a critical role of an interplay between Stag2 and Runx1 in the regulation of enhancer-promoter looping and transcription in hematopoiesis. Combined loss of Stag2 and Runx1, which co-localize at enhancer-rich, Ctcf-deficient sites, synergistically attenuates enhancer-promoter loops, particularly at sites enriched for RNA polymerase II and Mediator, and deregulates gene expression, leading to myeloid-skewed expansion of hematopoietic stem/progenitor cells (HSPCs) and myelodysplastic syndromes (MDS). Attenuated enhancer-promoter loops in Stag2/Runx1-deficient cells are associated with downregulation of genes with high basal transcriptional pausing, which are important for the regulation of HSPCs.　Down-regulation of high-pausing genes is also confirmed in STAG2/cohesin-mutated primary AML/MDS samples. Our results highlight a unique STAG2/RUNX1 interplay in gene regulation and provide insights into cohesin-mutated leukemogenesis.
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| |
|
| Overall design |
Comprehensive epigenome sequencing (RNA-seq, ATAC-seq, ChIP-seq and Hi-C) in WT, Stag2 knockout, Runx1 knockout, and double knockout cells.
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| |
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| Contributor(s) |
Ochi Y, Ogawa S |
| Citation(s) |
32249213 |
| |
| Submission date |
May 21, 2019 |
| Last update date |
Jul 07, 2020 |
| Contact name |
Yotaro Ochi |
| Organization name |
Kyoto Univiersity
|
| Department |
Department of Pathology and Tumor Biology
|
| Street address |
Yoshida-Konoe-cho
|
| City |
Kyoto |
| ZIP/Postal code |
606-8501 |
| Country |
Japan |
| |
|
| Platforms (2) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (16)
|
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| This SubSeries is part of SuperSeries: |
| GSE131583 |
Combined Cohesin-Runx1 Deficiency Synergistically Perturbs Chromatin Looping and Causes Myelodysplastic Syndromes |
|
| Relations |
| BioProject |
PRJNA544086 |
| SRA |
SRP199098 |
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