title: Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation.
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.
authors.affiliation: Department of Haematology, Cambridge Institute for Medical Research and Wellcome Trust and MRC Cambridge Stem Cell Institute, Cambridge CB2 0XY, UK.
authors.forename: Debbie K
authors.initials: DK
authors.lastname: Goode
authors.affiliation: Institute of Cancer end Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Birmingham B152TT, UK.
authors.forename: Nadine
authors.initials: N
authors.lastname: Obier
authors.affiliation: School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: M S
authors.initials: MS
authors.lastname: Vijayabaskar
authors.affiliation: CRUK Manchester Institute, University of Manchester, Manchester M20 4BX, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Lie-A-Ling
authors.affiliation: CRUK Manchester Institute, University of Manchester, Manchester M20 4BX, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lilly
authors.affiliation: Department of Haematology, Cambridge Institute for Medical Research and Wellcome Trust and MRC Cambridge Stem Cell Institute, Cambridge CB2 0XY, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hannah
authors.affiliation: Institute of Cancer end Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Birmingham B152TT, UK.
authors.forename: Monika
authors.initials: M
authors.lastname: Lichtinger
authors.affiliation: CRUK Manchester Institute, University of Manchester, Manchester M20 4BX, UK.
authors.forename: Kiran
authors.initials: K
authors.lastname: Batta
authors.affiliation: CRUK Manchester Institute, University of Manchester, Manchester M20 4BX, UK.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Florkowska
authors.affiliation: CRUK Manchester Institute, University of Manchester, Manchester M20 4BX, UK.
authors.forename: Rahima
authors.initials: R
authors.lastname: Patel
authors.affiliation: CRUK Manchester Institute, University of Manchester, Manchester M20 4BX, UK.
authors.forename: Mairi
authors.initials: M
authors.lastname: Challinor
authors.affiliation: CRUK Manchester Institute, University of Manchester, Manchester M20 4BX, UK.
authors.forename: Kirstie
authors.initials: K
authors.lastname: Wallace
authors.affiliation: Institute of Cancer end Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Birmingham B152TT, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Gilmour
authors.affiliation: Institute of Cancer end Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Birmingham B152TT, UK.
authors.forename: Salam A
authors.initials: SA
authors.lastname: Assi
authors.affiliation: Institute of Cancer end Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Birmingham B152TT, UK.
authors.forename: Pierre
authors.initials: P
authors.lastname: Cauchy
authors.affiliation: Institute of Cancer end Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Birmingham B152TT, UK.
authors.forename: Maarten
authors.initials: M
authors.lastname: Hoogenkamp
authors.affiliation: School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Westhead
authors.affiliation: CRUK Manchester Institute, University of Manchester, Manchester M20 4BX, UK.
authors.forename: Georges
authors.initials: G
authors.lastname: Lacaud
authors.affiliation: CRUK Manchester Institute, University of Manchester, Manchester M20 4BX, UK.
authors.forename: Valerie
authors.initials: V
authors.lastname: Kouskoff
authors.affiliation: Department of Haematology, Cambridge Institute for Medical Research and Wellcome Trust and MRC Cambridge Stem Cell Institute, Cambridge CB2 0XY, UK.
authors.forename: Berthold
authors.initials: B
authors.lastname: Göttgens
authors.affiliation: Institute of Cancer end Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Birmingham B152TT, UK. Electronic address: c.bonifer@bham.ac.uk.
authors.forename: Constanze
authors.initials: C
authors.lastname: Bonifer
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics*; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D018398:Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D011485:Protein Binding / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors