GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE131580 Query DataSets for GSE131580
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.
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)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (16)
GSM3790159 Hi-C_HSPC_BMT_WT_rep1
GSM3790160 Hi-C_HSPC_BMT_WT_rep2
GSM3790161 Hi-C_HSPC_BMT_SKO_rep1
This SubSeries is part of SuperSeries:
GSE131583 Combined Cohesin-Runx1 Deficiency Synergistically Perturbs Chromatin Looping and Causes Myelodysplastic Syndromes
BioProject PRJNA544086
SRA SRP199098

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
GSE131580_Hi-C_DKO_loop.bedpe.gz 175.2 Kb (ftp)(http) BEDPE
GSE131580_Hi-C_HL60_DKO_loop.bedpe.gz 105.6 Kb (ftp)(http) BEDPE
GSE131580_Hi-C_HL60_RKO_loop.bedpe.gz 222.1 Kb (ftp)(http) BEDPE
GSE131580_Hi-C_HL60_SKO_loop.bedpe.gz 140.6 Kb (ftp)(http) BEDPE
GSE131580_Hi-C_HL60_WT_loop.bedpe.gz 164.5 Kb (ftp)(http) BEDPE
GSE131580_Hi-C_RKO_loop.bedpe.gz 215.1 Kb (ftp)(http) BEDPE
GSE131580_Hi-C_SKO_loop.bedpe.gz 202.8 Kb (ftp)(http) BEDPE
GSE131580_Hi-C_WT_loop.bedpe.gz 194.9 Kb (ftp)(http) BEDPE
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap