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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Published in:	Developmental cell Vol. 36; no. 5; p. 572
Main Authors:	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
Language:	English
Published:	United States 07.03.2016
Subjects:	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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Abstract	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.
AbstractList	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.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. 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.
Author	Gilmour, Jane Bonifer, Constanze Hannah, Rebecca Lichtinger, Monika Batta, Kiran Westhead, David R Lilly, Andrew J Patel, Rahima Wallace, Kirstie Göttgens, Berthold Challinor, Mairi Obier, Nadine Assi, Salam A Vijayabaskar, M S Kouskoff, Valerie Hoogenkamp, Maarten Lacaud, Georges Goode, Debbie K Cauchy, Pierre Florkowska, Magdalena Lie-A-Ling, Michael
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SubjectTerms	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
Title	Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation
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