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| Status |
Public on Oct 07, 2010 |
| Title |
Combinatorial Transcriptional Control in Blood Stem/Progenitor Cells: Genome-wide Analysis of 10 major Transcriptional Regulators |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Combinatorial transcription factor (TF) interactions control cellular phenotypes and therefore underpin stem cell formation, maintenance and differentiation. Here we report the genome-wide binding patterns and combinatorial interactions for 10 key regulators of blood stem/progenitor cells (Scl/Tal1, Lyl1, Lmo2, Gata2, Runx1, Meis1, Pu.1, Erg, Fli-1, Gfi1b) thus providing the most comprehensive TF dataset for any adult stem/progenitor cell type to date. Genome-wide computational analysis of complex binding patterns followed by functional validation revealed the following: First, a previously unrecognized combinatorial interaction between a heptad of TFs (Scl, Lyl1, Lmo2, Gata2, Runx1, Erg, Fli-1). Second, we implicate direct protein-protein interactions between four key regulators (Runx1, Gata2, Scl, Erg) in stabilising complex binding to DNA. Third, Runx1+/-::Gata2+/- compound heterozygous mice are not viable with severe haematopoietic defects at midgestation. Taken together, this study demonstrates the power of genome-wide analysis in generating novel functional insights into the transcriptional control of stem and progenitor cells.
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| Overall design |
10 Samples (9 Transcription Factors and 1 Histone Modification) and 1 Control (IgG). All from the same cell line, a haematopoietic progenitor cell line (HPC-7).
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| Contributor(s) |
Wilson NK, Foster SD, Wang X, Knezevic K, Schütte J, Kinston S, Ouwehand WH, Dzierzak E, Pimanda JE, de Bruijn MF, Göttgens B |
| Citation(s) |
20887958, 21576367 |
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| Submission date |
Jun 07, 2010 |
| Last update date |
May 15, 2019 |
| Contact name |
Samuel David Foster |
| E-mail(s) |
sdf21@cam.ac.uk
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| Organization name |
Cambridge Institute for Medical Research
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| Department |
Department of Haematology
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| Lab |
Haematopoietic Stem Cell Lab
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| Street address |
Wellcome Trust/MRC Building, Addenbrooke's Hospital, Hills Road
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| City |
Cambridge |
| State/province |
Cambridgeshire |
| ZIP/Postal code |
CB2 0XY |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
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| Samples (11)
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| Relations |
| SRA |
SRP002575 |
| BioProject |
PRJNA127555 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE22178.tar.gz |
5.4 Mb |
(ftp)(http) |
TAR |
| GSE22178_RAW.tar |
5.3 Gb |
(http)(custom) |
TAR (of BEDGRAPH, TXT) |
| GSE22178_README.txt |
3.1 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Processed data provided as supplementary file |
| Raw data are available in SRA |
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