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| Status |
Public on May 18, 2010 |
| Title |
Genome-wide identification of SCL/Tal1’s functional targets; insights into its mechanisms of action in primary erythroid cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Coordination of cellular processes through the establishment of tissue-specific gene expression programmes is essential for lineage maturation. The basic helix-loop-helix haemopoietic transcriptional regulator SCL/Tal1 is required for terminal differentiation of red blood cells. To gain insight into SCL function and mechanisms of action in erythropoiesis, we performed ChIP-sequencing and gene expression analyses from primary fetal liver erythroid cells. We show that SCL coordinates expression of genes in most known red cell-specific processes. The majority of SCL’s genomic targets require direct DNA-binding activity. However, one fifth of SCL’s target sequences, mainly amongst those showing high affinity for SCL, can recruit the factor independently of its DNA binding activity. An unbiased DNA motif search of sequences bound by SCL identified CAGNTG as SCL-preferred E-box motif in erythroid cells. Novel motifs were also characterised that may help distinguish activated from repressed genes and suggest a new mechanism by which SCL may be recruited to DNA. Finally, analysis of recruitment of GATA1, a protein partner of SCL, to sequences occupied by SCL suggests that SCL’s binding is necessary prior or simultaneous to that of GATA1. This work provides the framework to study regulatory networks leading to erythroid terminal maturation and to model mechanisms of action of tissue-specific transcription factors.
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| Overall design |
Total RNA extracted from wild-type (WT) day E12.5 fetal liver Ter119- erythroid progenitor cells was compared to total RNA extracted from E12.5 fetal liver Ter119- cells expressing a DNA-binding mutant form of SCL (SclRER/RER).
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| Contributor(s) |
Kassouf M, Soneji S, Porcher C |
| Citation(s) |
20566737 |
| |
| Submission date |
May 17, 2010 |
| Last update date |
Jan 18, 2013 |
| Contact name |
Catherine Porcher |
| E-mail(s) |
catherine.porcher@imm.ox.ac.uk
|
| Phone |
44 (0)1865 222 309
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| Fax |
44 (0)1865 222 500
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| Organization name |
Oxford University
|
| Department |
Weatherall Institute of Molecular Medicine
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| Lab |
MRC Molecular Haematology Unit
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| Street address |
John Radcliffe Hospital
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| City |
Oxford |
| ZIP/Postal code |
OX2 7QG |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL6105 |
Illumina mouse-6 v1.1 expression beadchip |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA126841 |
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