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| Status |
Public on Jun 12, 2014 |
| Title |
A crucial role of the ubiquitously expressed transcription factor Sp1 at early stages of hematopoietic specification [ChIP-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Mammalian development is regulated by the interplay of tissue-specific and ubiquitously expressed transcription factors, such as Sp1. Sp1 knock-out mice die in utero with multiple phenotypic aberrations, but the underlying molecular mechanism of this differentiation failure has been elusive. Here we used conditional knock-out mice as well as the differentiation of mouse ES cells as a model to address this issue. To this end we examined differentiation potential, global gene expression patterns and Sp1 target regions in Sp1 wild-type and deficient cells representing different stages of hematopoiesis. Sp1-/- cells progress through most embryonic stages of blood cell development but cannot complete terminal differentiation. For most Sp1 target and non-target genes, gene expression is unaffected by Sp1 inactivation. However, Cdx and multiple Hox genes are stage-specific targets of Sp1 and are down-regulated at an early stage. As a consequence, expression of genes involved in hematopoietic specification are progressively deregulated, highlighting the regulatory hierarchy of hematopoietic specification. Our work demonstrates that the early absence of active Sp1 sets a cascade in motion that culminates in a failure of terminal hematopoietic differentiation and emphasizes the role of ubiquitously expressed transcription factors for tissue-specific gene regulation.
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| Overall design |
Two ChIP-Seq data from Sp1 transcription factor obtained from FLK+ and progenitor cells
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| Contributor(s) |
Gilmour J, Assi SA, Jaegle U, Kulu D, van de Werken H, Clarke D, Westhead DR, Philipsen S, Bonifer C |
| Citation(s) |
24850855 |
| |
| Submission date |
Nov 19, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Salam Adli Assi |
| E-mail(s) |
s.a.assi@bham.ac.uk
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| Organization name |
University of Birmingham
|
| Department |
Institute for Cancer and Genomic Sciences
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| Street address |
IBR
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| City |
Birmingham |
| ZIP/Postal code |
B15 2TT |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE52499 |
A crucial role of the ubiquitously expressed transcription factor Sp1 at early stages of hematopoietic specification |
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| Relations |
| BioProject |
PRJNA229111 |
| SRA |
SRP033120 |
