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Series GSE131581 Query DataSets for GSE131581
Status Public on Apr 07, 2020
Title Combined Cohesin-Runx1 Deficiency Synergistically Perturbs Chromatin Looping and Causes Myelodysplastic Syndromes [RNA-seq]
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
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.
 
Overall design Comprehensive epigenome sequencing (RNA-seq, ATAC-seq, ChIP-seq and Hi-C) in WT, Stag2 knockout, Runx1 knockout, and double knockout cells.
 
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)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (35)
GSM3790167 RNA_LSK_nonBMT_WT_rep1
GSM3790168 RNA_LSK_nonBMT_WT_rep2
GSM3790169 RNA_LSK_nonBMT_WT_rep3
This SubSeries is part of SuperSeries:
GSE131583 Combined Cohesin-Runx1 Deficiency Synergistically Perturbs Chromatin Looping and Causes Myelodysplastic Syndromes
Relations
BioProject PRJNA544088
SRA SRP199099

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE131581_HL60_cpm.txt.gz 540.6 Kb (ftp)(http) TXT
GSE131581_RNA_CMP_BMT_cpm.txt.gz 1.5 Mb (ftp)(http) TXT
GSE131581_RNA_CMP_nonBMT_cpm.txt.gz 609.3 Kb (ftp)(http) TXT
GSE131581_RNA_LSK_BMT_cpm.txt.gz 1.5 Mb (ftp)(http) TXT
GSE131581_RNA_LSK_nonBMT_cpm.txt.gz 635.9 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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