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Series GSE73215 Query DataSets for GSE73215
Status Public on Sep 21, 2015
Title Dose-dependent role of the cohesin complex in normal and malignant hematopoiesis [ATAC-Seq]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Cohesin complex members have recently been identified as putative tumor suppressors in hematologic and epithelial malignancies. The cohesin complex guides chromosome segregation, however cohesin-mutant leukemias do not show genomic instability. We hypothesized reduced cohesin function alters chromatin structure and disrupts cis-regulatory architecture of hematopoietic progenitors. We investigated the consequences of Smc3 deletion in normal and malignant hematopoiesis. Bi-allelic Smc3 loss induced bone marrow aplasia with premature sister chromatid separation, and revealed an absolute requirement for cohesin in hematopoietic stem cell function. In contrast, Smc3 haploinsufficiency increased self-renewal in vitro and in vivo including competitive transplantation. Smc3 haploinsufficiency reduced coordinated transcriptional output, including reduced expression of transcription factors and other genes associated with lineage commitment. Smc3 haploinsufficiency cooperated with Flt3-ITD to induce acute leukemia in vivo, with potentiated Stat5 signaling and altered nucleolar topology. These data establish a dose-dependency for cohesin in regulating chromatin structure and hematopoietic stem cell function.
Overall design ATAC-seq in murine c-kit+ cells for the following genotypes: Smc3 fl/+, Smc3 del/+, Flt3-ITD, Smc3 fl/del Flt3-ITD
Contributor(s) Ott CJ, Viny AD
Citation(s) 26438361
Submission date Sep 18, 2015
Last update date May 15, 2019
Contact name James Bradner
Organization name Dana-Farber Cancer Institute
Department Medical Oncology
Lab Bradner Lab
Street address 450 Brookline
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (8)
GSM1888841 Mxminus_Smc3fplus_ATAC_1
GSM1888842 Mxminus_Smc3fplus_ATAC_2
GSM1888843 Mxplus_Flt3ITD_ATAC_1
This SubSeries is part of SuperSeries:
GSE73218 Dose-dependent role of the cohesin complex in normal and malignant hematopoiesis
BioProject PRJNA296386
SRA SRP063874

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Supplementary file Size Download File type/resource
GSE73215_RAW.tar 7.5 Mb (http)(custom) TAR (of BED)
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Raw data are available in SRA
Processed data provided as supplementary file

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