title: Integrated genome-scale analysis of the transcriptional regulatory landscape in a blood stem/progenitor cell model.
abstract: Comprehensive study of transcriptional control processes will be required to enhance our understanding of both normal and malignant hematopoiesis. Modern sequencing technologies have revolutionized our ability to generate genome-scale expression and histone modification profiles, transcription factor (TF)-binding maps, and also comprehensive chromatin-looping information. Many of these technologies, however, require large numbers of cells, and therefore cannot be applied to rare hematopoietic stem/progenitor cell (HSPC) populations. The stem cell factor-dependent multipotent progenitor cell line HPC-7 represents a well-recognized cell line model for HSPCs. Here we report genome-wide maps for 17 TFs, 3 histone modifications, DNase I hypersensitive sites, and high-resolution promoter-enhancer interactomes in HPC-7 cells. Integrated analysis of these complementary data sets revealed TF occupancy patterns of genomic regions involved in promoter-anchored loops. Moreover, preferential associations between pairs of TFs bound at either ends of chromatin loops led to the identification of 4 previously unrecognized protein-protein interactions between key blood stem cell regulators. All HPC-7 data sets are freely available both through standard repositories and a user-friendly Web interface. Together with previously generated genome-wide data sets, this study integrates HPC-7 data into a genomic resource on par with ENCODE tier 1 cell lines and, importantly, is the only current model with comprehensive genome-scale data that is relevant to HSPC biology.
authors.affiliation: Department of Haematology, Wellcome Trust and Medical Research Council Cambridge Stem Cell Institute & Cambridge Institute for Medical Research, Cambridge University, Cambridge, United Kingdom; and.
authors.forename: Nicola K
authors.initials: NK
authors.lastname: Wilson
authors.affiliation: Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schoenfelder
authors.affiliation: Department of Haematology, Wellcome Trust and Medical Research Council Cambridge Stem Cell Institute & Cambridge Institute for Medical Research, Cambridge University, Cambridge, United Kingdom; and.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hannah
authors.affiliation: Department of Haematology, Wellcome Trust and Medical Research Council Cambridge Stem Cell Institute & Cambridge Institute for Medical Research, Cambridge University, Cambridge, United Kingdom; and.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez Castillo
authors.affiliation: Department of Haematology, Wellcome Trust and Medical Research Council Cambridge Stem Cell Institute & Cambridge Institute for Medical Research, Cambridge University, Cambridge, United Kingdom; and.
authors.forename: Judith
authors.initials: J
authors.lastname: Schütte
authors.affiliation: Department of Haematology, Wellcome Trust and Medical Research Council Cambridge Stem Cell Institute & Cambridge Institute for Medical Research, Cambridge University, Cambridge, United Kingdom; and.
authors.forename: Vasileios
authors.initials: V
authors.lastname: Ladopoulos
authors.affiliation: Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom.
authors.forename: Joanna
authors.initials: J
authors.lastname: Mitchelmore
authors.affiliation: Department of Haematology, Wellcome Trust and Medical Research Council Cambridge Stem Cell Institute & Cambridge Institute for Medical Research, Cambridge University, Cambridge, United Kingdom; and.
authors.forename: Debbie K
authors.initials: DK
authors.lastname: Goode
authors.affiliation: Department of Haematology, Wellcome Trust and Medical Research Council Cambridge Stem Cell Institute & Cambridge Institute for Medical Research, Cambridge University, Cambridge, United Kingdom; and.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Calero-Nieto
authors.affiliation: Department of Haematology, Wellcome Trust and Medical Research Council Cambridge Stem Cell Institute & Cambridge Institute for Medical Research, Cambridge University, Cambridge, United Kingdom; and.
authors.forename: Victoria
authors.initials: V
authors.lastname: Moignard
authors.affiliation: Department of Haematology, Wellcome Trust and Medical Research Council Cambridge Stem Cell Institute & Cambridge Institute for Medical Research, Cambridge University, Cambridge, United Kingdom; and.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Wilkinson
authors.affiliation: Department of Haematology, Wellcome Trust and Medical Research Council Cambridge Stem Cell Institute & Cambridge Institute for Medical Research, Cambridge University, Cambridge, United Kingdom; and.
authors.forename: Isabel
authors.initials: I
authors.lastname: Jimenez-Madrid
authors.affiliation: Department of Haematology, Wellcome Trust and Medical Research Council Cambridge Stem Cell Institute & Cambridge Institute for Medical Research, Cambridge University, Cambridge, United Kingdom; and.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kinston
authors.affiliation: Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Spivakov
authors.affiliation: Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Fraser
authors.affiliation: Department of Haematology, Wellcome Trust and Medical Research Council Cambridge Stem Cell Institute & Cambridge Institute for Medical Research, Cambridge University, Cambridge, United Kingdom; and.
authors.forename: Berthold
authors.initials: B
authors.lastname: Göttgens
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation; D016678:Genome; D057809:HEK293 Cells; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014157:Transcription Factors