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| Status |
Public on Sep 03, 2013 |
| Title |
Genome-wide Analysis of Transcriptional Regulators in Human Blood Stem/Progenitor Cells reveals a densely interconnected network of coding and non-coding genes. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Non-coding RNA profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Combinatorial transcription factor (TF) interactions regulate hematopoietic stem cell formation, maintenance and differentiation, and are increasingly recognised as drivers of stem cell signatures in cancer. However, genome-wide combinatorial binding patterns for key regulators do not exist in primary human hematopoietic stem/progenitor cells (HSPCs) and have constrained analysis of the global architecture of the molecular circuits controlling these cells. Here we provide new high-resolution genome-wide binding maps of seven key TFs (FLI1, ERG, GATA2, RUNX1, SCL, LYL1 and LMO2) in human CD34+ HSPCs together with quantitative RNA and microRNA expression profiles. We catalogue binding of TFs at coding genes and microRNA promoters and report that combinatorial binding of all seven TFs is favoured and is associated with differential expression of genes and microRNA in HSPCs. We also uncover a hitherto unrecognized association between FLI1 and RUNX1 pairing in HSPCs, establish a correlation between the density of histone modifications, which mark active enhancers and the number of overlapping TFs at a peak and identify complex relationships between specific miRNAs and coding genes regulated by the heptad. Taken together, this study demonstrates that a heptad of TFs forms a dense auto-regulatory core in human HSPCs with binding of all seven TFs at tissue specific regulatory elements of heptad genes and collectively regulates miRNAs that in turn target components of the heptad and genes regulated by the heptad.
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| Overall design |
Examination of cominatorial binding by 7 transcription factors, 1 IgG control along with mRNA and small RNA sequencing in human CD34+ cells
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| Contributor(s) |
Pimanda JE, Beck D, Wong JW |
| Citation(s) |
23974199 |
| Submission date |
Mar 13, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Jason Wong |
| E-mail(s) |
jason.wong@unsw.edu.au
|
| Organization name |
UNIVERSITY OF NEW SOUTH WALES
|
| Street address |
Level 2, Lowy Cancer Research Centre, University of New South Wales
|
| City |
Sydney |
| State/province |
NSW |
| ZIP/Postal code |
2052 |
| Country |
Australia |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA193088 |
| SRA |
SRP019263 |
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