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Status |
Public on Mar 31, 2015 |
Title |
β-catenin regulates primitive streak induction through collaborative interactions with SMAD2/3 and OCT4 |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Canonical Wnt and Nodal signaling are both required for induction of the primitive streak (PS), which guides organization of the early embryo. The Wnt effector β-catenin is thought to function in these early lineage specification decisions via transcriptional activation of Nodal signaling. Here, we demonstrate a broader role for β-catenin in PS formation by analyzing its genome-wide binding in a human embryonic stem cell model of PS induction. β-catenin occupies regulatory regions in numerous PS and neural crest genes, and direct interactions between β-catenin and the Nodal effectors SMAD2/3 are required at these regions for PS gene activation. Furthermore, OCT4 binding in proximity to these sites is likewise required for PS induction, suggesting a collaborative interaction between β-catenin and OCT4. Induction of neural crest genes by β-catenin is repressed by SMAD2/3, ensuring proper lineage specification. This study provides mechanistic insight into how Wnt signaling controls early cell lineage decisions.
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Overall design |
Examination of β-catenin binding in hESC incubated in media control (RPMI), media containing CHIR or CHIR+SB for 6h and analyzed by ChIP-sequencing
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Contributor(s) |
Funa N, Schachter K, Lerdrup M, Ekberg J, Hess K, Dietrich N, Honore C, Hansen K, Semb H |
Citation(s) |
25921273 |
Submission date |
Jun 13, 2014 |
Last update date |
May 15, 2019 |
Contact name |
Karen Schachter |
E-mail(s) |
karen.schachter@sund.ku.dk
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Organization name |
University of Copenhagen
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Department |
The Danish Stem Cell Center (DanStem)
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Lab |
Semb lab
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Street address |
Blegdamsvej 3B, building 6.4.24
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City |
Copenhagen N |
ZIP/Postal code |
2200 |
Country |
Denmark |
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Platforms (1) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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Samples (6)
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Relations |
BioProject |
PRJNA252723 |
SRA |
SRP043203 |