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Updated: May 2, 2026

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Chromatin Immunoprecipitation Assay for Tissue-specific Genes using Early-stage Mouse Embryos
Published on: April 29, 2011
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Charting Brachyury-mediated developmental pathways during early mouse embryogenesis.
Macarena Lolas1, Pablo D T Valenzuela, Robert Tjian
1Junior Fellow Program, Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147.
Summary
This study maps the Brachyury gene network, revealing its role as a transcriptional activator in early development. It highlights Brachyury
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Early embryogenesis involves complex lineage specification and morphogenetic processes.
- Brachyury is a key developmental regulator with a poorly understood genome-wide function.
Purpose of the Study:
- To systematically identify transcriptional programs regulated by Brachyury.
- To elucidate the Brachyury-dependent gene regulatory network and its role in development.
Main Methods:
- Chromosomal localization mapping using ChIP sequencing and ChIP-exonuclease.
- Genome-wide in vitro and in vivo perturbation analysis.
- Cross-species evolutionary comparison and mRNA-sequencing correlation analysis.
Main Results:
- Identified Brachyury-bound enhancers with distinct sequence signatures.
- Unveiled a detailed Brachyury-dependent gene-regulatory network.
- Demonstrated Brachyury functions primarily as a transcriptional activator, including a feedback loop with Foxa2 and Sox17 for stem cell commitment.
Conclusions:
- Brachyury directly influences diverse developmental pathways and cellular housekeeping programs.
- The Brachyury-Foxa2-Sox17 feedback loop is critical for stem cell lineage commitment.
- Brachyury is crucial for up-regulating hematopoietic and muscle-fate regulators, ensuring developmental homeostasis.

