Dual roles for MEF2A and MEF2D during human macrophage terminal differentiation and c-Jun expression
| Autor: | Véronique Collin-Faure, Thierry Rabilloud, Claudie Lemercier, Daniel Hanau, Huguette Bausinger, Catherine Aude-Garcia |
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| Přispěvatelé: | Biochimie et biophysique des systèmes intégrés (BBSI), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2010 |
| Předmět: |
Transcriptional Activation
Proto-Oncogene Proteins c-jun MADS Domain Proteins Biochemistry Histone Deacetylases 03 medical and health sciences 0302 clinical medicine Histone H2A medicine Humans Molecular Biology 030304 developmental biology 0303 health sciences biology MEF2 Transcription Factors Histone deacetylase 2 Macrophages Life Sciences HDAC7 Cell Differentiation Cell Biology Histone acetyltransferase Molecular biology Chromatin Trichostatin A Gene Expression Regulation Myogenic Regulatory Factors 030220 oncology & carcinogenesis biology.protein Histone deacetylase Myelopoiesis Protein Binding medicine.drug |
| Zdroj: | Biochemical Journal Biochemical Journal, Portland Press, 2010, 430 (2), pp.237-244. ⟨10.1042/BJ20100131⟩ Biochemical Journal, 2010, 430 (2), pp.237-244. ⟨10.1042/BJ20100131⟩ |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bj20100131 |
| Popis: | International audience; Recent reports have evidenced a role for the Myocyte Enhancer Factor 2C (MEF2C) in myelopoiesis, although the precise functions of this transcription factor are still unclear. We show here 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 immunopoprecipitations 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 Trichostatin A, a 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 analyzed the potential interaction of MEF2A with p300 histone acetyltransferase, whose expression is upregulated 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 human macrophages, as activator or as repressor of gene transcription. |
| Databáze: | OpenAIRE |
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