@article {6894,
	title = {Charting Brachyury-mediated developmental pathways during early mouse embryogenesis.},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	volume = {111},
	year = {2014},
	month = {2014 Mar 10},
	pages = {4478-83},
	abstract = {<p>To gain insights into coordinated lineage-specification and morphogenetic processes during early embryogenesis, here we report a systematic identification of transcriptional programs mediated by a key developmental regulator-Brachyury. High-resolution chromosomal localization mapping of Brachyury by ChIP sequencing and ChIP-exonuclease revealed distinct sequence signatures enriched in Brachyury-bound enhancers. A combination of genome-wide in vitro and in vivo perturbation analysis and cross-species evolutionary comparison unveiled a detailed Brachyury-dependent gene-regulatory network that directly links the function of Brachyury to diverse developmental pathways and cellular housekeeping programs. We also show that Brachyury functions primarily as a transcriptional activator genome-wide and that an unexpected gene-regulatory feedback loop consisting of Brachyury, Foxa2, and Sox17 directs proper stem-cell lineage commitment during streak formation. Target gene and mRNA-sequencing correlation analysis of the T(c) mouse model supports a crucial role of Brachyury in up-regulating multiple key hematopoietic and muscle-fate regulators. Our results thus chart a comprehensive map of the Brachyury-mediated gene-regulatory network and how it influences in vivo developmental homeostasis and coordination.</p>
},
	issn = {1091-6490},
	doi = {10.1073/pnas.1402612111},
	author = {Lolas, Macarena and Valenzuela, Pablo D T and Tjian, Robert and Liu, Zhe}
}
