Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation

Metazoan development involves the successive activation and silencing of specific gene expression programs and is driven by tissue-specific transcription factors programming the chromatin landscape. To understand how this process executes an entire developmental pathway, we generated global gene exp...

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Veröffentlicht in:	Developmental cell Jg. 36; H. 5; S. 572
Hauptverfasser:	Goode, Debbie K, Obier, Nadine, Vijayabaskar, M S, Lie-A-Ling, Michael, Lilly, Andrew J, Hannah, Rebecca, Lichtinger, Monika, Batta, Kiran, Florkowska, Magdalena, Patel, Rahima, Challinor, Mairi, Wallace, Kirstie, Gilmour, Jane, Assi, Salam A, Cauchy, Pierre, Hoogenkamp, Maarten, Westhead, David R, Lacaud, Georges, Kouskoff, Valerie, Göttgens, Berthold, Bonifer, Constanze
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 07.03.2016
Schlagworte:	Animals Cell Differentiation - genetics Cell Lineage - physiology Embryonic Stem Cells - cytology Gene Expression Regulation, Developmental - genetics Gene Regulatory Networks - genetics Hematopoiesis - physiology Hematopoietic Stem Cells - cytology Homeodomain Proteins - metabolism Mice Protein Binding - genetics Transcription Factors - metabolism
ISSN:	1878-1551, 1878-1551
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Zusammenfassung:	Metazoan development involves the successive activation and silencing of specific gene expression programs and is driven by tissue-specific transcription factors programming the chromatin landscape. To understand how this process executes an entire developmental pathway, we generated global gene expression, chromatin accessibility, histone modification, and transcription factor binding data from purified embryonic stem cell-derived cells representing six sequential stages of hematopoietic specification and differentiation. Our data reveal the nature of regulatory elements driving differential gene expression and inform how transcription factor binding impacts on promoter activity. We present a dynamic core regulatory network model for hematopoietic specification and demonstrate its utility for the design of reprogramming experiments. Functional studies motivated by our genome-wide data uncovered a stage-specific role for TEAD/YAP factors in mammalian hematopoietic specification. Our study presents a powerful resource for studying hematopoiesis and demonstrates how such data advance our understanding of mammalian development.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1878-1551 1878-1551
DOI:	10.1016/j.devcel.2016.01.024