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| Status |
Public on Jan 01, 2015 |
| Title |
Scl specifies hemogenic endothelium and inhibits cardiogenesis via primed enhancers [ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| 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 |
ChIP-seq with Scl, Hand1, Lsd1, Ezh2, H3K4me1 and H3K27ac in different cell types with mesodermal origin. Scl ChIP-seq in WT, SclKO, SclKO-iScl and Gata12KO mES cell derived day4 EB (embryoid body) Flk1+ mesodermal cells, SclKO-iScl ES cells and MEL cells; Hand1 ChIP-seq in WT mES cell derived day4 EB Flk1+ mesodermal cells; Lsd1 and Ezh2 ChIP-seq in WT and SclKO mES cell derived day4 EB Flk1+ mesodermal cells. ChIP-seq of histone modifications H3K4me1 and H3K27ac in WT, SclKO and Gata12KO mES cell derived day4 EB Flk1+ mesodermal cells, HPC7 hematopoietic progenitor cells and HL1 cardiomyogenic cells
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| Contributor(s) |
Org T, Duan D, Ferrari R, Montel-Hagen A, Van Handel B, Kerényi MA, Sasidharan R, Fujiwara Y, Rubbi L, Pellegrini M, Orkin SH, Kurdistani SK, Mikkola HH |
| Citation(s) |
25564442 |
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| Submission date |
May 19, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Tõnis Org |
| E-mail(s) |
toniso@ut.ee
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| Phone |
372-52-11484
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| Organization name |
University of Tartu
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| Department |
Institute of Molecular and Cell Biology
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| Lab |
Biotechnology
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| Street address |
Riia 23
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| City |
Tartu |
| ZIP/Postal code |
51010 |
| Country |
Estonia |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (34)
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| This SubSeries is part of SuperSeries: |
| GSE47085 |
Scl specifies hemogenic endothelium and inhibits cardiogenesis via primed enhancers |
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| Relations |
| BioProject |
PRJNA203513 |
| SRA |
SRP022897 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE47082_RAW.tar |
2.2 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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