title: Pioneering Activity of the C-Terminal Domain of EBF1 Shapes the Chromatin Landscape for B Cell Programming.
abstract: Lymphopoiesis requires the activation of lineage-specific genes embedded in naive, inaccessible chromatin or in primed, accessible chromatin. The mechanisms responsible for de novo gain of chromatin accessibility, known as "pioneer" function, remain poorly defined. Here, we showed that the EBF1 C-terminal domain (CTD) is required for the regulation of a specific gene set involved in B cell fate decision and differentiation, independently of activation and repression functions. Using genome-wide analysis of DNaseI hypersensitivity and DNA methylation in multipotent Ebf1(-/-) progenitors and derivative EBF1wt- or EBF1ΔC-expressing cells, we found that the CTD promoted chromatin accessibility and DNA demethylation in previously naive chromatin. The CTD allowed EBF1 to bind at inaccessible genomic regions that offer limited co-occupancy by other transcription factors, whereas the CTD was dispensable for EBF1 binding at regions that are occupied by multiple transcription factors. Thus, the CTD enables EBF1 to confer permissive lineage-specific changes in progenitor chromatin landscape.
authors.affiliation: Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Boller
authors.affiliation: Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Ramamoorthy
authors.affiliation: Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
authors.forename: Duygu
authors.initials: D
authors.lastname: Akbas
authors.affiliation: Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Nechanitzky
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; Swiss Institute of Bioinformatics, 4058 Basel, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Burger
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Rabih
authors.initials: R
authors.lastname: Murr
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schübeler
authors.affiliation: Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany. Electronic address: grosschedl@ie-freiburg.mpg.de.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Grosschedl
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D019175:DNA Methylation / Q000235:genetics; D053263:Gene Regulatory Networks / Q000235:genetics; D054503:Lymphoid Progenitor Cells / Q000502:physiology*; D038041:Lymphopoiesis; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017434:Protein Structure, Tertiary / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; C081976:EBF1 protein, human; D015534:Trans-Activators
keywords: B lymphopoiesis; DNA methylation; DNaseI hypersensitivity; EBF1; chromatin; pioneer transcription factor