C/EBPα Activates Pre-existing and De Novo Macrophage Enhancers during Induced Pre-B Cell Transdifferentiation and Myelopoiesis
Transcription-factor-induced somatic cell conversions are highly relevant for both basic and clinical research yet their mechanism is not fully understood and it is unclear whether they reflect normal differentiation processes. Here we show that during pre-B-cell-to-macrophage transdifferentiation,...
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doaj-81118c959b7845b3bf40d7b33d8d1cd92020-11-24T21:03:01ZengElsevierStem Cell Reports2213-67112015-08-015223224710.1016/j.stemcr.2015.06.007C/EBPα Activates Pre-existing and De Novo Macrophage Enhancers during Induced Pre-B Cell Transdifferentiation and MyelopoiesisChris van Oevelen0Samuel Collombet1Guillermo Vicent2Maarten Hoogenkamp3Cyrille Lepoivre4Aimee Badeaux5Lars Bussmann6Jose Luis Sardina7Denis Thieffry8Miguel Beato9Yang Shi10Constanze Bonifer11Thomas Graf12Center for Genomic Regulation and Pompeu Fabra University, 08003 Barcelona, SpainEcole Normale Supérieure, Institut de Biologie de l’ENS, INSERM, U1024, Centre National de la Recherche Scientifique (CNRS) 8197, 75005 Paris, FranceCenter for Genomic Regulation and Pompeu Fabra University, 08003 Barcelona, SpainSchool of Cancer Sciences, Institute of Biomedical Research, University of Birmingham, Birmingham B15 2TT, UKCNRS, Aix-Marseille Université, IGS UMR7256, 13288 Marseille, FranceHarvard Medical School, Children’s Hospital, Boston, MA 02115, USACenter for Genomic Regulation and Pompeu Fabra University, 08003 Barcelona, SpainCenter for Genomic Regulation and Pompeu Fabra University, 08003 Barcelona, SpainEcole Normale Supérieure, Institut de Biologie de l’ENS, INSERM, U1024, Centre National de la Recherche Scientifique (CNRS) 8197, 75005 Paris, FranceCenter for Genomic Regulation and Pompeu Fabra University, 08003 Barcelona, SpainHarvard Medical School, Children’s Hospital, Boston, MA 02115, USASchool of Cancer Sciences, Institute of Biomedical Research, University of Birmingham, Birmingham B15 2TT, UKCenter for Genomic Regulation and Pompeu Fabra University, 08003 Barcelona, SpainTranscription-factor-induced somatic cell conversions are highly relevant for both basic and clinical research yet their mechanism is not fully understood and it is unclear whether they reflect normal differentiation processes. Here we show that during pre-B-cell-to-macrophage transdifferentiation, C/EBPα binds to two types of myeloid enhancers in B cells: pre-existing enhancers that are bound by PU.1, providing a platform for incoming C/EBPα; and de novo enhancers that are targeted by C/EBPα, acting as a pioneer factor for subsequent binding by PU.1. The order of factor binding dictates the upregulation kinetics of nearby genes. Pre-existing enhancers are broadly active throughout the hematopoietic lineage tree, including B cells. In contrast, de novo enhancers are silent in most cell types except in myeloid cells where they become activated by C/EBP factors. Our data suggest that C/EBPα recapitulates physiological developmental processes by short-circuiting two macrophage enhancer pathways in pre-B cells.http://www.sciencedirect.com/science/article/pii/S2213671115001885 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chris van Oevelen Samuel Collombet Guillermo Vicent Maarten Hoogenkamp Cyrille Lepoivre Aimee Badeaux Lars Bussmann Jose Luis Sardina Denis Thieffry Miguel Beato Yang Shi Constanze Bonifer Thomas Graf |
spellingShingle |
Chris van Oevelen Samuel Collombet Guillermo Vicent Maarten Hoogenkamp Cyrille Lepoivre Aimee Badeaux Lars Bussmann Jose Luis Sardina Denis Thieffry Miguel Beato Yang Shi Constanze Bonifer Thomas Graf C/EBPα Activates Pre-existing and De Novo Macrophage Enhancers during Induced Pre-B Cell Transdifferentiation and Myelopoiesis Stem Cell Reports |
author_facet |
Chris van Oevelen Samuel Collombet Guillermo Vicent Maarten Hoogenkamp Cyrille Lepoivre Aimee Badeaux Lars Bussmann Jose Luis Sardina Denis Thieffry Miguel Beato Yang Shi Constanze Bonifer Thomas Graf |
author_sort |
Chris van Oevelen |
title |
C/EBPα Activates Pre-existing and De Novo Macrophage Enhancers during Induced Pre-B Cell Transdifferentiation and Myelopoiesis |
title_short |
C/EBPα Activates Pre-existing and De Novo Macrophage Enhancers during Induced Pre-B Cell Transdifferentiation and Myelopoiesis |
title_full |
C/EBPα Activates Pre-existing and De Novo Macrophage Enhancers during Induced Pre-B Cell Transdifferentiation and Myelopoiesis |
title_fullStr |
C/EBPα Activates Pre-existing and De Novo Macrophage Enhancers during Induced Pre-B Cell Transdifferentiation and Myelopoiesis |
title_full_unstemmed |
C/EBPα Activates Pre-existing and De Novo Macrophage Enhancers during Induced Pre-B Cell Transdifferentiation and Myelopoiesis |
title_sort |
c/ebpα activates pre-existing and de novo macrophage enhancers during induced pre-b cell transdifferentiation and myelopoiesis |
publisher |
Elsevier |
series |
Stem Cell Reports |
issn |
2213-6711 |
publishDate |
2015-08-01 |
description |
Transcription-factor-induced somatic cell conversions are highly relevant for both basic and clinical research yet their mechanism is not fully understood and it is unclear whether they reflect normal differentiation processes. Here we show that during pre-B-cell-to-macrophage transdifferentiation, C/EBPα binds to two types of myeloid enhancers in B cells: pre-existing enhancers that are bound by PU.1, providing a platform for incoming C/EBPα; and de novo enhancers that are targeted by C/EBPα, acting as a pioneer factor for subsequent binding by PU.1. The order of factor binding dictates the upregulation kinetics of nearby genes. Pre-existing enhancers are broadly active throughout the hematopoietic lineage tree, including B cells. In contrast, de novo enhancers are silent in most cell types except in myeloid cells where they become activated by C/EBP factors. Our data suggest that C/EBPα recapitulates physiological developmental processes by short-circuiting two macrophage enhancer pathways in pre-B cells. |
url |
http://www.sciencedirect.com/science/article/pii/S2213671115001885 |
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