Trichostatin A decreases the levels of MeCP2 expression and phosphorylation and increases its chromatin binding affinity
| Autor: | Kristal Missiaen, Manjinder S. Cheema, Gilda Stefanelli, Alexia Martínez de Paz, Katrina V. Good, Alan Underhill, Nicoletta Landsberger, Oliver A. Krupke, Monica Tyagi, Taylor L. Gretzinger, Michael J. Hendzel, Juan Ausió, Anita A. Thambirajah, Robert L. Chow |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research congenital hereditary and neonatal diseases and abnormalities Methyl-CpG-Binding Protein 2 Hydroxamic Acids MECP2 03 medical and health sciences Mice mental disorders medicine Animals Humans Phosphorylation Molecular Biology biology Chromatin binding 3T3 Cells Chromatin 3. Good health Cell biology nervous system diseases Histone Deacetylase Inhibitors 030104 developmental biology Histone Trichostatin A HEK293 Cells Acetylation biology.protein Histone deacetylase Protein Processing Post-Translational medicine.drug HeLa Cells Protein Binding Research Paper |
| Zdroj: | Epigenetics. 12(11) |
| ISSN: | 1559-2308 |
| Popis: | MeCP2 binds to methylated DNA in a chromatin context and has an important role in cancer and brain development and function. Histone deacetylase (HDAC) inhibitors are currently being used to palliate many cancer and neurological disorders. Yet, the molecular mechanisms involved are not well known for the most part and, in particular, the relationship between histone acetylation and MeCP2 is not well understood. In this paper, we study the effect of the HDAC inhibitor trichostatin A (TSA) on MeCP2, a protein whose dysregulation plays an important role in these diseases. We find that treatment of cells with TSA decreases the phosphorylation state of this protein and appears to result in a higher MeCP2 chromatin binding affinity. Yet, the binding dynamics with which the protein binds to DNA appear not to be significantly affected despite the chromatin reorganization resulting from the high levels of acetylation. HDAC inhibition also results in an overall decrease in MeCP2 levels of different cell lines. Moreover, we show that miR132 increases upon TSA treatment, and is one of the players involved in the observed downregulation of MeCP2. |
| Databáze: | OpenAIRE |
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