Dendritic cell development requires histone deacetylase activity
| العنوان: | Dendritic cell development requires histone deacetylase activity |
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| المؤلفون: | Piritta Felker, Nina Rehage, Saskia Mitzka, Stefan Rose-John, Caroline Küstermann, Kristin Seré, Heike Chauvistré, Theresa Klisch, Martin Zenke |
| المصدر: | European Journal of Immunology |
| بيانات النشر: | BlackWell Publishing Ltd, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | STAT3 Transcription Factor, Histone acetylation and deacetylation, Immunology, Gene Expression, Mice, SCID, Dendritic cells, Histone Deacetylases, chemistry.chemical_compound, Mice, HDAC, Mice, Inbred NOD, Proto-Oncogene Proteins, Immunology and Allergy, Animals, Flt3, Cells, Cultured, Histone deacetylase 5, biology, Gene Expression Profiling, Stem Cells, PU.1, hemic and immune systems, Acetylation, Cell Differentiation, Chromatin, Mice, Inbred C57BL, Histone, chemistry, Histone acetylation, fms-Like Tyrosine Kinase 3, Interferon Regulatory Factors, biology.protein, Cancer research, Trans-Activators, Histone deacetylase activity, Histone deacetylase, IRF8, Molecular Immunology, Signal Transduction |
| الوصف: | DCs develop from multipotent progenitors (MPPs), which commit into DC-restricted common dendritic cell progenitors (CDPs). CDPs further differentiate into classical DCs (cDCs) and plasmacytoid DCs (pDCs). Here, we studied the impact of histone acetylation on DC development in C57BL/6 mice by interfering with histone acetylation and deacetylation, employing histone deacetylase (HDAC) inhibitors. We observed that commitment of MPPs into CDPs was attenuated by HDAC inhibition and that pDC development was specifically blocked. Gene expression profiling revealed that HDAC inhibition prevents establishment of a DC-specific gene expression repertoire. Importantly, protein levels of the core DC transcription factor PU.1 were reduced in HDAC inhibitor-treated cells and consequently PU.1 recruitment at PU.1 target genes Fms-like tyrosine kinase 3 (Flt3), interferon regulatory factor 8 (IRF8), and PU.1 itself was impaired. Thus, our results demonstrate that attenuation of PU.1 expression by HDAC inhibition causes reduced expression of key DC regulators, which results in attenuation of DC development. We propose that chromatin modifiers, such as HDACs, are required for establishing a DC gene network, where Flt3/STAT3 signaling drives PU.1 and IRF8 expression and DC development. Taken together, our study identifies HDACs as critical regulators of DC lineage commitment and development. |
| اللغة: | English |
| تدمد: | 1521-4141 0014-2980 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6061865de3a8a3e174918eb59134008eTest http://europepmc.org/articles/PMC4209797Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6061865de3a8a3e174918eb59134008e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15214141 00142980 |
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