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Series GSE184490 Query DataSets for GSE184490
Status Public on Dec 16, 2021
Title Dynamic Runx1 chromatin boundaries affect gene expression in hematopoietic development
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Other
Summary The transcription factor RUNX1 is a critical regulator of developmental hematopoiesis and is frequently disrupted in leukemia. Runx1 is a large, complex gene that is expressed from two alternative promoters under the spatiotemporal control of multiple hematopoietic enhancers. To dissect the dynamic regulation of Runx1 in hematopoietic development, we analyzed its three-dimensional chromatin conformation in mouse embryonic stem cell (ESC) differentiation cultures. Runx1 resides in a 1.1 Mb topologically associating domain (TAD) demarcated by convergent CTCF motifs. As ESCs differentiate to mesoderm, chromatin accessibility, Runx1 enhancer-promoter (E-P) interactions, and CTCF-CTCF interactions increased in the TAD, along with initiation of Runx1 expression from the P2 promoter. Differentiation to hematopoietic progenitor cells was associated with the formation of tissue-specific sub-TADs over Runx1, a shift in E-P interactions, P1 promoter demethylation, and robust expression from both Runx1 promoters. Deletions of promoter-proximal CTCF sites at the sub-TAD boundaries had no obvious effects on E-P interactions but led to partial loss of domain structure, mildly affected gene expression, and delayed hematopoietic development. Together, our analyses of gene regulation at a large multi-promoter developmental gene revealed that dynamic sub-TAD chromatin boundaries play a role in establishing TAD structure and coordinated gene expression.
 
Overall design Tiled-C, poly-A-minus-RNA-seq, ATAC-seq, CTCF-ChIP-seq
 
Contributor(s) Owens DD, Anselmi G, Hughes JR, de Bruijn MF
Citation(s) 35140205
Submission date Sep 20, 2021
Last update date Mar 09, 2022
Contact name Dominic Owens
E-mail(s) dominic.owens@utoronto.ca
Organization name University of Oxford
Department MRC WIMM
Street address John Radcliffe Hospital
City Oxford
ZIP/Postal code OX3 9DS
Country United Kingdom
 
Platforms (2)
GPL16417 Illumina MiSeq (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (132)
GSM5590037 Tiled-C_P1-CTCF-KO_Undiff_bioRep_E7.1_seqRun1
GSM5590038 Tiled-C_P1-CTCF-KO_Undiff_bioRep_E7.2_seqRun1
GSM5590039 Tiled-C_P1-CTCF-KO_Undiff_bioRep_E9.1_seqRun1
Relations
BioProject PRJNA764773
SRA SRP337972

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
GSE184490_416B_Ctcf_merge_0.02_peaks.bed.gz 355.9 Kb (ftp)(http) BED
GSE184490_ATAC-seq_peaks_Wild-type_CD41.bed.gz 231.6 Kb (ftp)(http) BED
GSE184490_ATAC-seq_peaks_Wild-type_Flk1.bed.gz 596.3 Kb (ftp)(http) BED
GSE184490_BigWig.tar.gz 752.6 Mb (ftp)(http) TAR
GSE184490_Bisulfite-seq__methCpG_Wild-type_416B.bedGraph.gz 3.4 Kb (ftp)(http) BEDGRAPH
GSE184490_Bisulfite-seq__methCpG_Wild-type_E14.bedGraph.gz 3.7 Kb (ftp)(http) BEDGRAPH
GSE184490_Bisulfite-seq__methCpG_Wild-type_In-vitro-methylated-control.bedGraph.gz 3.5 Kb (ftp)(http) BEDGRAPH
GSE184490_Tiled-C_Iced_Matrix.tar.gz 105.0 Mb (ftp)(http) TAR
GSE184490_s2_features_counts_mm9_Owens.txt.gz 853.9 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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