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Dev Cell. 2016 Mar 7;36(5):572-87. doi: 10.1016/j.devcel.2016.01.024. Epub 2016 Feb 25.

Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation.

Author information

1
Department of Haematology, Cambridge Institute for Medical Research and Wellcome Trust and MRC Cambridge Stem Cell Institute, Cambridge CB2 0XY, UK.
2
Institute of Cancer end Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Birmingham B152TT, UK.
3
School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
4
CRUK Manchester Institute, University of Manchester, Manchester M20 4BX, UK.
5
Institute of Cancer end Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Birmingham B152TT, UK. Electronic address: c.bonifer@bham.ac.uk.

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.

PMID:
26923725
PMCID:
PMC4780867
DOI:
10.1016/j.devcel.2016.01.024
[Indexed for MEDLINE]
Free PMC Article

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