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Series GSE129478 Query DataSets for GSE129478
Status Public on Apr 09, 2019
Title Cohesin-dependent regulation of dynamic gene expression during differentiation is lost in Cohesin-mutated myeloid malignancies
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary The Cohesin complex critically controls interactions between proximal and distal cis-regulatory elements, while Cohesin disruption causes improper gene activation. This process associates with biased hematopoiesis, and Cohesin mutations are common in myeloid neoplasia. In this study, we initially explore Cohesin-associated dynamics and regulation of hematopoietic stem cell renewal and erythropoiesis. Cohesin binding to chromatin increases during erythroid differentiation at active promoters and enhancers only, with pre-binding of Etv6 predicting the subsequent dynamics of Cohesin binding at these elements. Etv6 also binds with the Cohesin complex at chromatin during haematopoiesis. Perturbation of Cohesin members does not alter hematopoietic self-renewal, but severely impairs erythroid differentiation. As in normal erythroid differentiation, the strongest impairment of gene activation in Cohesin-perturbed erythropoiesis occurs at Etv6-pre-bound loci. Taken together these findings propose a mechanism for how the Cohesin complex regulates the induction of gene expression during differentiation and how this may be perturbed in myeloid malignancies.
Overall design Integrative analysis of Cohesin-associated cis-regulatory units (ChIP Seq, RNA Seq, promoter Capture HiC in HSPC and Erythroid cells
Contributor(s) Sasca D, Huntly B
Citation(s) 31515253
Submission date Apr 08, 2019
Last update date Jan 17, 2021
Contact name Daniel Sasca
Organization name University Medical Center Mainz
Department III. Medical Department
Street address Langenbeckstr 1
City Mainz
ZIP/Postal code 55131
Country Germany
Platforms (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (74)
GSM3713679 Luc1_HPC_RNA-seq (inhibitor)
GSM3713680 Luc2_HPC_RNA-seq (inhibitor)
GSM3713681 Luc3_HPC_RNA-seq (inhibitor)
BioProject PRJNA531471
SRA SRP191444

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
GSE129478_HPC1_and_HPC2_washU_text.txt.gz 1.1 Mb (ftp)(http) TXT
GSE129478_Luc1_and_Luc2_Ery_washU_text.txt.gz 1.3 Mb (ftp)(http) TXT
GSE129478_RAW.tar 7.6 Gb (http)(custom) TAR (of BEDGRAPH, TXT)
GSE129478_shStag2_1_and_2_Ery_washU_text.txt.gz 1.3 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data provided as supplementary file

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