title: Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells.
abstract: Differentiated macrophages can self-renew in tissues and expand long term in culture, but the gene regulatory mechanisms that accomplish self-renewal in the differentiated state have remained unknown. Here we show that in mice, the transcription factors MafB and c-Maf repress a macrophage-specific enhancer repertoire associated with a gene network that controls self-renewal. Single-cell analysis revealed that, in vivo, proliferating resident macrophages can access this network by transient down-regulation of Maf transcription factors. The network also controls embryonic stem cell self-renewal but is associated with distinct embryonic stem cell-specific enhancers. This indicates that distinct lineage-specific enhancer platforms regulate a shared network of genes that control self-renewal potential in both stem and mature cells.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France. Centre de Recherche en Cancerologie de Marseille, INSERM (U1068), CNRS (U7258), Université Aix-Marseille (UM105), Marseille, France. sieweke@ciml.univ-mrs.fr erinn.soucie@inserm.fr arend@stanford.edu.
authors.forename: Erinn L
authors.initials: EL
authors.lastname: Soucie
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA 94305-5324, USA.
authors.forename: Ziming
authors.initials: Z
authors.lastname: Weng
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France.
authors.forename: Laufey
authors.initials: L
authors.lastname: Geirsdóttir
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France. Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft, 10 Robert-Rössle-Strasse, 13125 Berlin, Germany.
authors.forename: Kaaweh
authors.initials: K
authors.lastname: Molawi
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Maurizio
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Fenouil
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France.
authors.forename: Noushine
authors.initials: N
authors.lastname: Mossadegh-Keller
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France.
authors.forename: Gregory
authors.initials: G
authors.lastname: Gimenez
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: VanHille
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France.
authors.forename: Meryam
authors.initials: M
authors.lastname: Beniazza
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Favret
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Berruyer
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Perrin
authors.affiliation: Broad Institute of Harvard University and MIT, Cambridge, MA 02142, USA.
authors.forename: Nir
authors.initials: N
authors.lastname: Hacohen
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France. Institut de Génétique Moléculaire de Montpellier, CNRS UMR 5535, 1919 Route de Mende, 34293 Montpellier, France.
authors.forename: J-C
authors.initials: JC
authors.lastname: Andrau
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Ferrier
authors.affiliation: Centre de Recherche en Cancerologie de Marseille, INSERM (U1068), CNRS (U7258), Université Aix-Marseille (UM105), Marseille, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Dubreuil
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA 94305-5324, USA. Department of Genetics, Stanford University, Stanford, CA 94305, USA. sieweke@ciml.univ-mrs.fr erinn.soucie@inserm.fr arend@stanford.edu.
authors.forename: Arend
authors.initials: A
authors.lastname: Sidow
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France. Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft, 10 Robert-Rössle-Strasse, 13125 Berlin, Germany. sieweke@ciml.univ-mrs.fr erinn.soucie@inserm.fr arend@stanford.edu.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Sieweke
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D053595:Embryonic Stem Cells / Q000166:cytology*; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D008264:Macrophages / Q000166:cytology*; D051258:MafB Transcription Factor / Q000378:metabolism; D051379:Mice; D051257:Proto-Oncogene Proteins c-maf / Q000378:metabolism; D059010:Single-Cell Analysis; D015533:Transcriptional Activation
chemical_list: C495608:Maf protein, mouse; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D051257:Proto-Oncogene Proteins c-maf