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| Status |
Public on Jan 01, 2015 |
| Title |
Scl specifies hemogenic endothelium and inhibits cardiogenesis via primed enhancers [expression] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Scl/Tal1 confers hemogenic competence and prevents cardiomyogenesis in embryonic endothelium. Here we show that Scl both directly activates a broad gene regulatory network required for hematopoietic stem/progenitor cell (HS/PC) development, and represses transcriptional regulators required for cardiogenesis. Cardiac repression occurs during a short developmental window through Scl binding to distant cardiac enhancers that harbor H3K4me1 at this stage. Scl binding to hematopoietic regulators extends throughout HS/PC and erythroid development and spreads from distant enhancers to promoters. Surprisingly, Scl complex partners Gata 1 and 2 are dispensable for hematopoietic versus cardiac specification and Scl binding to the majority of its target genes. Nevertheless, Gata factors co-operate with Scl to activate selected transcription factors to facilitate HS/PC emergence from hemogenic endothelium. These results uncover a dual function for Scl in dictating hematopoietic versus cardiac fate choice and suggest a mechanism by which lineage-specific bHLH factors direct the divergence of competing fates.
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| Overall design |
Examination of Scl target genes in ES cell derived day4 EB (embryoid body) Flk+ mesodermal cells
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| Contributor(s) |
Org T, Duan D, Ferrari R, Montel-Hagen A, Van Handel B, Kerényi MA, Sasidharan R, Rubbi L, Fujiwara Y, Pellegrini M, Orkin SH, Kurdistani SK, Mikkola HK |
| Citation(s) |
25564442 |
| |
| Submission date |
May 19, 2013 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Tõnis Org |
| E-mail(s) |
toniso@ut.ee
|
| Phone |
372-52-11484
|
| Organization name |
University of Tartu
|
| Department |
Institute of Molecular and Cell Biology
|
| Lab |
Biotechnology
|
| Street address |
Riia 23
|
| City |
Tartu |
| ZIP/Postal code |
51010 |
| Country |
Estonia |
| |
|
| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE47085 |
Scl specifies hemogenic endothelium and inhibits cardiogenesis via primed enhancers |
|
| Relations |
| BioProject |
PRJNA203511 |
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