Recent reports have evidenced a role for MEF2C (myocyte enhancer factor 2C) in myelopoiesis, although the precise functions of this transcription factor are still unclear. We show in the present study that MEF2A and MEF2D, two other MEF2 family members, are expressed in human primary monocytes and in higher amounts in monocyte-derived macrophages. High levels of MEF2A–MEF2D heterodimers are found in macrophage-differentiated HL60 cells. Chromatin immunoprecipitations demonstrate that MEF2A is present on the c-Jun promoter, both in undifferentiated and in macrophage-differentiated cells. Moreover, c-Jun expression is derepressed in undifferentiated cells in the presence of HDAC (histone deacetylase) inhibitor, indicating the importance of chromatin acetylation in this process. We show that MEF2A/D dimers strongly interact with HDAC1, and to a lesser extent with HDAC7 in macrophages, whereas low levels of MEF2A/D–HDAC1 complexes are found in undifferentiated cells or in monocytes. Since trichostatin A does not disrupt MEF2A/D–HDAC1 complexes, we analysed the potential interaction of MEF2A with p300 histone acetyltransferase, whose expression is up-regulated in macrophages. Interestingly, endogenous p300 only associates with MEF2A in differentiated macrophages, indicating that MEF2A/D could activate c-Jun expression in macrophages through a MEF2A/D–p300 activator complex. The targets of MEF2A/D–HDAC1–HDAC7 multimers remain to be identified. Nevertheless, these data highlight for the first time the possible dual roles of MEF2A and MEF2D in human macrophages, as activators or as repressors of gene transcription.
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Research Article|
August 13 2010
Dual roles for MEF2A and MEF2D during human macrophage terminal differentiation and c-Jun expression
Catherine Aude-Garcia;
Catherine Aude-Garcia
1
*CEA, DSV, iRTSV, Laboratoire BBSI, F-38054 Grenoble, France
†CNRS, UMR 5092, F-38054 Grenoble, France
‡Université Joseph Fourier Grenoble 1, France
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Véronique Collin-Faure;
Véronique Collin-Faure
1
*CEA, DSV, iRTSV, Laboratoire BBSI, F-38054 Grenoble, France
†CNRS, UMR 5092, F-38054 Grenoble, France
‡Université Joseph Fourier Grenoble 1, France
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Huguette Bausinger;
Huguette Bausinger
§Inserm Unité 725 “Biology of Human Dendritic Cells”, F-67065 Strasbourg, France
∥Etablissement Français du Sang-Alsace, F-67065 Strasbourg, France
¶Université de Strasbourg, F-67000 Strasbourg, France
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Daniel Hanau;
Daniel Hanau
§Inserm Unité 725 “Biology of Human Dendritic Cells”, F-67065 Strasbourg, France
∥Etablissement Français du Sang-Alsace, F-67065 Strasbourg, France
¶Université de Strasbourg, F-67000 Strasbourg, France
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Thierry Rabilloud;
Thierry Rabilloud
*CEA, DSV, iRTSV, Laboratoire BBSI, F-38054 Grenoble, France
†CNRS, UMR 5092, F-38054 Grenoble, France
‡Université Joseph Fourier Grenoble 1, France
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Claudie Lemercier
Claudie Lemercier
2
*CEA, DSV, iRTSV, Laboratoire BBSI, F-38054 Grenoble, France
†CNRS, UMR 5092, F-38054 Grenoble, France
‡Université Joseph Fourier Grenoble 1, France
2To whom correspondence should be addressed (e-mail claudie.lemercier@cea.fr).
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Publisher: Portland Press Ltd
Received:
February 10 2010
Revision Received:
June 14 2010
Accepted:
July 01 2010
Accepted Manuscript online:
July 01 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 430 (2): 237–244.
Article history
Received:
February 10 2010
Revision Received:
June 14 2010
Accepted:
July 01 2010
Accepted Manuscript online:
July 01 2010
Citation
Catherine Aude-Garcia, Véronique Collin-Faure, Huguette Bausinger, Daniel Hanau, Thierry Rabilloud, Claudie Lemercier; Dual roles for MEF2A and MEF2D during human macrophage terminal differentiation and c-Jun expression. Biochem J 1 September 2010; 430 (2): 237–244. doi: https://doi.org/10.1042/BJ20100131
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